Age-Specific Difference in Pulmonary Cellular Injury and Mitochondrial Damage

  • Katherine L. Tuggle
  • Michelle V. FanucchiEmail author
Part of the Respiratory Medicine book series (RM, volume 15)


The impact of lung-targeted toxicants on the respiratory system of developing and aging animals is not well defined, let alone the role that mitochondria may play in the cascade of factors involved in cellular injury. Environmentally induced pulmonary cell injury is often due to exposure to bioactivated toxicants or oxidant gases. The major defense mechanisms against these insults are the antioxidant and xenobiotic-metabolizing enzymes. The age-specific expression of these enzymes and their roles in protecting the lung from specific toxicants is discussed as well as the interrelationship with mitochondrial function. A review of the literature reveals evidence of the mitochondrial involvement in cellular injury during lung development and aging. Whether the alterations of mitochondria are critical early steps in lung injury or an outcome of a cascade of processes during lung development and aging is not clear at this time.


Lung development Lung aging Mitochondria mtDNA Antioxidant Tobacco smoke Ozone Hyperoxia 


  1. 1.
    Gottlieb RA. Mitochondria: execution central. FEBS Lett. 2000;482:6–12.PubMedGoogle Scholar
  2. 2.
    Murphy MP. How mitochondria produce reactive oxygen species. Biochem J. 2009;417:1–13. England.PubMedCentralPubMedGoogle Scholar
  3. 3.
    Scatena R, Bottoni P, Botta G, Martorana GE, Giardina B. The role of mitochondria in pharmacotoxicology: a reevaluation of an old, newly emerging topic. Am J Physiol Cell Physiol. 2007;293:C12–21.PubMedGoogle Scholar
  4. 4.
    Wallace KB, Starkov AA. Mitochondrial targets of drug toxicity. Annu Rev Pharmacol Toxicol. 2000;40:353–88.PubMedGoogle Scholar
  5. 5.
    Chance B, Sies H, Boveris A. Hydroperoxide metabolism in mammalian organs. Physiol Rev. 1979;59:527–605.PubMedGoogle Scholar
  6. 6.
    Kwong LK, Sohal RS. Substrate and site specificity of hydrogen peroxide generation in mouse mitochondria. Arch Biochem Biophys. 1998;350:118–26.PubMedGoogle Scholar
  7. 7.
    Boveris A, Chance B. The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. Biochem J. 1973;134:707–16.PubMedCentralPubMedGoogle Scholar
  8. 8.
    de Grey AD. The reductive hotspot hypothesis: an update. Arch Biochem Biophys. 2000;373:295–301.PubMedGoogle Scholar
  9. 9.
    Sastre J, Pallardó FV, García de la Asunción J, Viña J. Mitochondria, oxidative stress and aging. Free Radic Res. 2000;32:189–98.PubMedGoogle Scholar
  10. 10.
    Mammucari C, Rizzuto R. Signaling pathways in mitochondrial dysfunction and aging. Mech Ageing Dev. 2010;131:536–43.PubMedCentralPubMedGoogle Scholar
  11. 11.
    Saraste M. Oxidative phosphorylation at the fin de siecle. Science. 1999;283:1488–93.PubMedGoogle Scholar
  12. 12.
    Halestrap A. Biochemistry: a pore way to die. Nature. 2005;434:578–9. England.PubMedGoogle Scholar
  13. 13.
    Leist M, Single B, Castoldi AF, Kuhnle S, Nicotera P. Intracellular adenosine triphosphate (atp) concentration: a switch in the decision between apoptosis and necrosis. J Exp Med. 1997;185:1481–6.PubMedCentralPubMedGoogle Scholar
  14. 14.
    Duchen MR. Roles of mitochondria in health and disease. Diabetes. 2004;53 Suppl 1:S96–102.PubMedGoogle Scholar
  15. 15.
    Massaro GD, Massaro D. Development of bronchiolar epithelium in rats. Am J Physiol. 1986;250:R783–8.PubMedGoogle Scholar
  16. 16.
    Young SL, Fram EK, Spain CL, Larson EW. Development of type ii pneumocytes in rat lung. Am J Physiol. 1991;260:L113–22.PubMedGoogle Scholar
  17. 17.
    Hyde DM, Plopper CG, Kass PH, Alley JL. Estimation of cell numbers and volumes of bronchiolar epithelium during rabbit lung maturation. Am J Anat. 1983;167:359–70.PubMedGoogle Scholar
  18. 18.
    Plopper CG, Alley JL, Serabjitsingh CJ, Philpot RM. Cytodifferentiation of the nonciliated bronchiolar epithelial (clara) cell during rabbit lung maturation: an ultrastructural and morphometric study. Am J Anat. 1983;167:329–57.PubMedGoogle Scholar
  19. 19.
    de Grey AD. A proposed refinement of the mitochondrial free radical theory of aging. Bioessays. 1997;19:161–6.PubMedGoogle Scholar
  20. 20.
    Harman D. The biologic clock: the mitochondria? J Am Geriatr Soc. 1972;20:145–7.PubMedGoogle Scholar
  21. 21.
    Atamna H, Robinson C, Ingersoll R, Elliott H, Ames BN. N-t-butyl hydroxylamine is an antioxidant that reverses age-related changes in mitochondria in vivo and in vitro. FASEB J. 2001;15:2196–204.PubMedGoogle Scholar
  22. 22.
    Brown WM, George Jr M, Wilson AC. Rapid evolution of animal mitochondrial dna. Proc Natl Acad Sci U S A. 1979;76:1967–71.PubMedCentralPubMedGoogle Scholar
  23. 23.
    Johns DR. Seminars in medicine of the beth israel hospital, boston. Mitochondrial dna and disease. N Engl J Med. 1995;333:638–44.PubMedGoogle Scholar
  24. 24.
    Balaban RS, Nemoto S, Finkel T. Mitochondria, oxidants, and aging. Cell. 2005;120:483–95.PubMedGoogle Scholar
  25. 25.
    Liu P, Demple B. Dna repair in mammalian mitochondria: much more than we thought? Environ Mol Mutagen. 2010;51:417–26.PubMedGoogle Scholar
  26. 26.
    Gaziev AI, Shaikhaev GO. Lesions of the mitochondrial genome and ways of its preservation. Genetika. 2008;44:437–55.PubMedGoogle Scholar
  27. 27.
    Gadaleta MN, Rainaldi G, Lezza AM, Milella F, Fracasso F, Cantatore P. Mitochondrial dna copy number and mitochondrial dna deletion in adult and senescent rats. Mutat Res. 1992;275:181–93.PubMedGoogle Scholar
  28. 28.
    Lee HC, Lu CY, Fahn HJ, Wei YH. Aging- and smoking-associated alteration in the relative content of mitochondrial dna in human lung. FEBS Lett. 1998;441:292–6.PubMedGoogle Scholar
  29. 29.
    Davies KJ. Oxidative stress, antioxidant defenses, and damage removal, repair, and replacement systems. IUBMB Life. 2000;50:279–89.PubMedGoogle Scholar
  30. 30.
    Dobson AW, Grishko V, LeDoux SP, Kelley MR, Wilson GL, Gillespie MN. Enhanced mtdna repair capacity protects pulmonary artery endothelial cells from oxidant-mediated death. Am J Physiol Lung Cell Mol Physiol. 2002;283:L205–10.PubMedGoogle Scholar
  31. 31.
    Ruchko M, Gorodnya O, LeDoux SP, Alexeyev MF, Al-Mehdi AB, Gillespie MN. Mitochondrial dna damage triggers mitochondrial dysfunction and apoptosis in oxidant-challenged lung endothelial cells. Am J Physiol Lung Cell Mol Physiol. 2005;288:L530–5.PubMedGoogle Scholar
  32. 32.
    Masuyama M, Iida R, Takatsuka H, Yasuda T, Matsuki T. Quantitative change in mitochondrial dna content in various mouse tissues during aging. Biochim Biophys Acta. 2005;1723: 302–8.PubMedGoogle Scholar
  33. 33.
    Yowe DL, Ames BN. Quantitation of age-related mitochondrial dna deletions in rat tissues shows that their pattern of accumulation differs from that of humans. Gene. 1998;209:23–30.PubMedGoogle Scholar
  34. 34.
    Sohal RS, Sohal BH. Hydrogen peroxide release by mitochondria increases during aging. Mech Ageing Dev. 1991;57:187–202.PubMedGoogle Scholar
  35. 35.
    Sohal RS, Dubey A. Mitochondrial oxidative damage, hydrogen peroxide release, and aging. Free Radic Biol Med. 1994;16:621–6.PubMedGoogle Scholar
  36. 36.
    Chance B, Williams GR. Respiratory enzymes in oxidative phosphorylation. Iii. The steady state. J Biol Chem. 1955;217:409–27.PubMedGoogle Scholar
  37. 37.
    Ochoa S. Efficiency of aerobic phosphorylation in cell-free heart extracts. J Biol Chem. 1943;151:493–505.Google Scholar
  38. 38.
    Acuna-Castroviejo D, Carretero M, Doerrier C, Lopez LC, Garcia-Corzo L, Tresguerres JA, et al. Melatonin protects lung mitochondria from aging. Age (Dordr). 2012;34:681–92.Google Scholar
  39. 39.
    Zychlinski L, Raska-Emery P, Balis JU, Montgomery MR. Age-related difference in bioenergetics of lung and heart mitochondrial from rats exposed to ozone. J Biochem Toxicol. 1989;4:251–4.PubMedGoogle Scholar
  40. 40.
    Servais S, Boussouar A, Molnar A, Douki T, Pequignot JM, Favier R. Age-related sensitivity to lung oxidative stress during ozone exposure. Free Radical Research. 2005;39:305–16.PubMedGoogle Scholar
  41. 41.
    Zeltner TB, Burri PH. The postnatal development and growth of the human lung. Ii. Morphology. Respir Physiol. 1987;67:269–82.PubMedGoogle Scholar
  42. 42.
    Zeltner TB, Caduff JH, Gehr P, Pfenninger J, Burri PH. The postnatal development and growth of the human lung. I. Morphometry. Respir Physiol. 1987;67:247–67.PubMedGoogle Scholar
  43. 43.
    Vaz Fragoso CA, Gill TM. Respiratory impairment and the aging lung: a novel paradigm for assessing pulmonary function. J Gerontol A Biol Sci Med Sci. 2012;67:264–75.PubMedGoogle Scholar
  44. 44.
    Wang L, Green FH, Smiley-Jewell SM, Pinkerton KE. Susceptibility of the aging lung to environmental injury. Semin Respir Crit Care Med. 2010;31:539–53.PubMedGoogle Scholar
  45. 45.
    D’Errico A, Scarani P, Colosimo E, Spina M, Grigioni WF, Mancini AM. Changes in the alveolar connective tissue of the ageing lung. An immunohistochemical study. Virchows Arch A Pathol Anat Histopathol. 1989;415:137–44.PubMedGoogle Scholar
  46. 46.
    Campisi J, d’Adda di Fagagna F. Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol. 2007;8:729–40.PubMedGoogle Scholar
  47. 47.
    Hoeijmakers JH. Dna damage, aging, and cancer. N Engl J Med. 2009;361:1475–85.PubMedGoogle Scholar
  48. 48.
    Zhang Y, Chong E, Herman B. Age-associated increases in the activity of multiple caspases in fisher 344 rat organs. Exp Gerontol. 2002;37:777–89.PubMedGoogle Scholar
  49. 49.
    McElroy MC, Postle AD, Kelly FJ. Catalase, superoxide dismutase and glutathione peroxidase activities of lung and liver during human development. Biochim Biophys Acta. 1992;1117:153–8.PubMedGoogle Scholar
  50. 50.
    Asayama K, Hayashibe H, Dobashi K, Uchida N, Kobayashi M, Kawaoi A, et al. Immunohistochemical study on perinatal development of rat superoxide dismutases in lungs and kidneys. Pediatr Res. 1991;29:487–91.PubMedGoogle Scholar
  51. 51.
    Clerch LB, Massaro D. Rat lung antioxidant enzymes: differences in perinatal gene expression and regulation. Am J Physiol. 1992;263:L466–70.PubMedGoogle Scholar
  52. 52.
    Frank L, Sosenko IR. Development of lung antioxidant enzyme system in late gestation: possible implications for the prematurely born infant. J Pediatr. 1987;110:9–14.PubMedGoogle Scholar
  53. 53.
    Frank L, Price LT, Whitney PL. Possible mechanism for late gestational development of the antioxidant enzymes in the fetal rat lung. Biol Neonate. 1996;70:116–27.PubMedGoogle Scholar
  54. 54.
    Hayashibe H, Asayama K, Dobashi K, Kato K. Prenatal development of antioxidant enzymes in rat lung, kidney, and heart: marked increase in immunoreactive superoxide dismutases, glutathione peroxidase, and catalase in the kidney. Pediatr Res. 1990;27:472–5.PubMedGoogle Scholar
  55. 55.
    Rickett GM, Kelly FJ. Developmental expression of antioxidant enzymes in guinea pig lung and liver. Development. 1990;108:331–6.PubMedGoogle Scholar
  56. 56.
    Sosenko IR, Frank L. Thyroid inhibition and developmental increases in fetal rat lung antioxidant enzymes. Am J Physiol. 1989;257:L94–9.PubMedGoogle Scholar
  57. 57.
    Tanswell AK, Tzaki MG, Byrne PJ. Hormonal and local factors influence antioxidant enzyme activity of rat fetal lung cells in vitro. Exp Lung Res. 1986;11:49–59.PubMedGoogle Scholar
  58. 58.
    Walther FJ, Ikegami M, Warburton D, Polk DH. Corticosteroids, thyrotropin-releasing hormone, and antioxidant enzymes in preterm lamb lungs. Pediatr Res. 1991;30:518–21.PubMedGoogle Scholar
  59. 59.
    Weisiger RA, Fridovich I. Superoxide dismutase. Organelle specificity. J Biol Chem. 1973;248:3582–92.PubMedGoogle Scholar
  60. 60.
    Weisiger RA, Fridovich I. Mitochondrial superoxide simutase. Site of synthesis and intramitochondrial localization. J Biol Chem. 1973;248:4793–6.PubMedGoogle Scholar
  61. 61.
    Crapo JD, Oury T, Rabouille C, Slot JW, Chang LY. Copper, zinc superoxide dismutase is primarily a cytosolic protein in human cells. Proc Natl Acad Sci U S A. 1992;89:10405–9.PubMedCentralPubMedGoogle Scholar
  62. 62.
    Marklund SL. Extracellular superoxide dismutase in human tissues and human cell lines. J Clin Invest. 1984;74:1398–403.PubMedCentralPubMedGoogle Scholar
  63. 63.
    Oury TD, Crapo JD, Valnickova Z, Enghild JJ. Human extracellular superoxide dismutase is a tetramer composed of two disulphide-linked dimers: a simplified, high-yield purification of extracellular superoxide dismutase. Biochem J. 1996;317(Pt 1):51–7.PubMedCentralPubMedGoogle Scholar
  64. 64.
    Huie RE, Padmaja S. The reaction of no with superoxide. Free Radic Res Commun. 1993;18:195–9.PubMedGoogle Scholar
  65. 65.
    Nozik-Grayck E, Dieterle CS, Piantadosi CA, Enghild JJ, Oury TD. Secretion of extracellular superoxide dismutase in neonatal lungs. Am J Physiol Lung Cell Mol Physiol. 2000;279:L977–84.PubMedGoogle Scholar
  66. 66.
    Strange RC, Cotton W, Fryer AA, Drew R, Bradwell AR, Marshall T, et al. Studies on the expression of cu, zn superoxide dismutase in human tissues during development. Biochim Biophys Acta. 1988;964:260–5.PubMedGoogle Scholar
  67. 67.
    Hass MA, Massaro D. Developmental regulation of rat lung cu, zn-superoxide dismutase. Biochem J. 1987;246:697–703.PubMedCentralPubMedGoogle Scholar
  68. 68.
    Kakkar P, Jaffery FN, Viswanathan PN. Neonatal developmental pattern of superoxide dismutase and aniline hydroxylase in rat lung. Environ Res. 1986;41:302–8.PubMedGoogle Scholar
  69. 69.
    Levonen AL, Lapatto R, Saksela M, Raivio KO. Expression of gamma-glutamylcysteine synthetase during development. Pediatr Res. 2000;47:266–70.PubMedGoogle Scholar
  70. 70.
    Stevens JB, Autor AP. Proposed mechanism for neonatal rat tolerance to normobaric hyperoxia. Fed Proc. 1980;39:3138–43.PubMedGoogle Scholar
  71. 71.
    Fanucchi MV. Development of antioxidant and xenobiotic metabolizing enzyme systems. In: Harding R, Pinkerton KE, Plopper CG, editors. The lung development, aging, and the environment. London: Elsevier; 2004. p. 177–85.Google Scholar
  72. 72.
    Tanswell AK, Freeman BA. Differentiation-arrested rat fetal lung in primary monolayer cell culture. Iii. Antioxidant enzyme activity. Exp Lung Res. 1984;6:149–58.PubMedGoogle Scholar
  73. 73.
    Chen Y, Frank L. Differential gene expression of antioxidant enzymes in the perinatal rat lung. Pediatr Res. 1993;34:27–31.PubMedGoogle Scholar
  74. 74.
    de Haan JB, Tymms MJ, Cristiano F, Kola I. Expression of copper/zinc superoxide dismutase and glutathione peroxidase in organs of developing mouse embryos, fetuses, and neonates. Pediatr Res. 1994;35:188–96.PubMedGoogle Scholar
  75. 75.
    Mamo LB, Suliman HB, Giles BL, Auten RL, Piantadosi CA, Nozik-Grayck E. Discordant extracellular superoxide dismutase expression and activity in neonatal hyperoxic lung. Am J Respir Crit Care Med. 2004;170:313–8.PubMedGoogle Scholar
  76. 76.
    Santa María C, Ayala A, Revilla E. Changes in superoxide dismutase activity in liver and lung of old rats. Free Radic Res. 1996;25:401–5.PubMedGoogle Scholar
  77. 77.
    Hatao H, Oh-ishi S, Itoh M, Leeuwenburgh C, Ohno H, Ookawara T, et al. Effects of acute exercise on lung antioxidant enzymes in young and old rats. Mech Ageing Dev. 2006;127:384–90.PubMedGoogle Scholar
  78. 78.
    Amicarelli F, Di Ilio C, Masciocco L, Bonfigli A, Zarivi O, D’Andrea MR, et al. Aging and detoxifying enzymes responses to hypoxic or hyperoxic treatment. Mech Ageing Dev. 1997;97:215–26.PubMedGoogle Scholar
  79. 79.
    Canada AT, Herman LA, Young SL. An age-related difference in hyperoxia lethality: role of lung antioxidant defense mechanisms. Am J Physiol. 1995;268:L539–45.PubMedGoogle Scholar
  80. 80.
    Perez R, Lopez M, Barja de Quiroga G. Aging and lung antioxidant enzymes, glutathione, and lipid peroxidation in the rat. Free Radic Biol Med. 1991;10:35–9.PubMedGoogle Scholar
  81. 81.
    Ramesh T, Kim SW, Sung JH, Hwang SY, Sohn SH, Yoo SK, et al. Effect of fermented panax ginseng extract (ginst) on oxidative stress and antioxidant activities in major organs of aged rats. Exp Gerontol. 2012;47:77–84.PubMedGoogle Scholar
  82. 82.
    Frank L. Developmental aspects of experimental pulmonary oxygen toxicity. Free Radic Biol Med. 1991;11:463–94.PubMedGoogle Scholar
  83. 83.
    Schisler NJ, Singh SM. Inheritance and expression of tissue-specific catalase activity during development and aging in mice. Genome. 1987;29:748–60.PubMedGoogle Scholar
  84. 84.
    Raza H. Dual localization of glutathione s-transferase in the cytosol and mitochondria: implications in oxidative stress, toxicity and disease. FEBS J. 2011;278:4243–51.PubMedCentralPubMedGoogle Scholar
  85. 85.
    Meister A. Glutathione, metabolism and function via the gamma-glutamyl cycle. Life Sci. 1974;15:177–90.PubMedGoogle Scholar
  86. 86.
    Meister A. Selective modification of glutathione metabolism. Science. 1983;220:472–7.PubMedGoogle Scholar
  87. 87.
    Meister A, Anderson ME. Glutathione. Annu Rev Biochem. 1983;52:711–60.PubMedGoogle Scholar
  88. 88.
    Melikian AA, Bagheri K, Hecht SS, Hoffmann D. Metabolism of benzo[a]pyrene and 7 beta,8 alpha-dihydroxy-9 alpha, 10 alpha-epoxy-7,8,9,10-tetrahydrobenzo[a pyrene in lung and liver of newborn mice. Chemico-Biological Interactions. 1989;69:245–57.PubMedGoogle Scholar
  89. 89.
    Deneke SM, Fanburg BL. Regulation of cellular glutathione. Am J Physiol. 1989;257:L163–73.PubMedGoogle Scholar
  90. 90.
    Eke BC, Vural N, Işcan M. Age dependent differential effects of cigarette smoke on hepatic and pulmonary xenobiotic metabolizing enzymes in rats. Arch Toxicol. 1997;71:696–702.PubMedGoogle Scholar
  91. 91.
    Martensson J, Jain A, Stole E, Frayer W, Auld PA, Meister A. Inhibition of glutathione synthesis in the newborn rat: a model for endogenously produced oxidative stress. Proc Natl Acad Sci U S A. 1991;88:9360–4.PubMedCentralPubMedGoogle Scholar
  92. 92.
    Oakes SM, Takahashi Y, Williams MC, Joyce-Brady M. Ontogeny of gamma-glutamyltransferase in the rat lung. Am J Physiol. 1997;272:L739–44.PubMedGoogle Scholar
  93. 93.
    Langley-Evans SC, Wood S, Jackson AA. Enzymes of the gamma-glutamyl cycle are programmed in utero by maternal nutrition. Ann Nutr Metab. 1995;39:28–35.PubMedGoogle Scholar
  94. 94.
    Lavoie JC, Spalinger M, Chessex P. Glutathione synthetic activity in the lungs in newborn guinea pigs. Lung. 1999;177:1–7.PubMedGoogle Scholar
  95. 95.
    Bottje WG, Wang S, Beers KW, Cawthon D. Lung lining fluid antioxidants in male broilers: age-related changes under thermoneutral and cold temperature conditions. Poult Sci. 1998;77:1905–12.PubMedGoogle Scholar
  96. 96.
    Gould NS, Min E, Gauthier S, Chu HW, Martin R, Day BJ. Aging adversely affects the cigarette smoke-induced glutathione adaptive response in the lung. Am J Respir Crit Care Med. 2010;182:1114–22.PubMedCentralPubMedGoogle Scholar
  97. 97.
    Drost EM, Skwarski KM, Sauleda J, Soler N, Roca J, Agusti A, et al. Oxidative stress and airway inflammation in severe exacerbations of copd. Thorax. 2005;60:293–300.PubMedCentralPubMedGoogle Scholar
  98. 98.
    de la Asuncion JG, Millan A, Pla R, Bruseghini L, Esteras A, Pallardo FV, et al. Mitochondrial glutathione oxidation correlates with age-associated oxidative damage to mitochondrial dna. FASEB J. 1996;10:333–8.PubMedGoogle Scholar
  99. 99.
    Pacht ER, Davis WB. Role of transferrin and ceruloplasmin in antioxidant activity of lung epithelial lining fluid. J Appl Physiol. 1988;64:2092–9.PubMedGoogle Scholar
  100. 100.
    Yang F, Friedrichs WE, deGraffenried L, Herbert DC, Weaker FJ, Bowman BH, et al. Cellular expression of ceruloplasmin in baboon and mouse lung during development and inflammation. Am J Respir Cell Mol Biol. 1996;14:161–9.PubMedGoogle Scholar
  101. 101.
    Das KC, Pahl PM, Guo XL, White CW. Induction of peroxiredoxin gene expression by oxygen in lungs of newborn primates. Am J Respir Cell Mol Biol. 2001;25:226–32.PubMedGoogle Scholar
  102. 102.
    Vyas JR, Currie A, Dunster C, Kelly FJ, Kotecha S. Ascorbate acid concentration in airways lining fluid from infants who develop chronic lung disease of prematurity. Eur J Pediatr. 2001;160:177–84.PubMedGoogle Scholar
  103. 103.
    Rikans LE, Moore DR. Effect of aging on aqueous-phase antioxidants in tissues of male fischer rats. Biochim Biophys Acta. 1988;966:269–75.PubMedGoogle Scholar
  104. 104.
    Vincent R, Vu D, Hatch G, Poon R, Dreher K, Guénette J, et al. Sensitivity of lungs of aging fischer 344 rats to ozone: assessment by bronchoalveolar lavage. Am J Physiol. 1996;271: L555–65.PubMedGoogle Scholar
  105. 105.
    Buckpitt A, Chang AM, Weir A, Van Winkle L, Duan X, Philpot R, et al. Relationship of cytochrome p450 activity to clara cell cytotoxicity. Iv. Metabolism of naphthalene and naphthalene oxide in microdissected airways from mice, rats, and hamsters. Mol Pharmacol. 1995;47:74–81.PubMedGoogle Scholar
  106. 106.
    Buckpitt AR, Franklin RB. Relationship of naphthalene and 2-methylnaphthalene metabolism to pulmonary bronchiolar epithelial cell necrosis. Pharmacol Ther. 1989;41:393–410.PubMedGoogle Scholar
  107. 107.
    Statham CN, Boyd MR. Distribution and metabolism of the pulmonary alkylating agent and cytotoxin, 4-ipomeanol, in control and diethylmaleate-treated rats. Biochem Pharmacol. 1982;31:1585–9.PubMedGoogle Scholar
  108. 108.
    Verschoyle RD, Carthew P, Wolf CR, Dinsdale D. 1-Nitronaphthalene toxicity in rat lung and liver: effects of inhibiting and inducing cytochrome p450 activity. Toxicol Appl Pharmacol. 1993;122:208–13.PubMedGoogle Scholar
  109. 109.
    Dutcher JS, Boyd MR. Species and strain differences in target organ alkylation and toxicity by 4-ipomeanol. Predictive value of covalent binding in studies of target organ toxicities by reactive metabolites. Biochem Pharmacol. 1979;28:3367–72.PubMedGoogle Scholar
  110. 110.
    Boyd MR, Statham CN, Longo NS. The pulmonary clara cell as a target for toxic chemicals requiring metabolic activation; studies with carbon tetrachloride. J Pharmacol Exp Ther. 1980;212:109–14.PubMedGoogle Scholar
  111. 111.
    Moussa M, Forkert PG. 1,1-Dichloroethylene-induced alterations in glutathione and covalent binding in murine lung: morphological, histochemical, and biochemical studies. J Pathol. 1992;166:199–207.PubMedGoogle Scholar
  112. 112.
    Reid WD, Ilett KF, Glick JM, Krishna G. Metabolism and binding of aromatic hydrocarbons in the lung. Relationship to experimental bronchiolar necrosis. Am Rev Respir Dis. 1973;107:539–51.PubMedGoogle Scholar
  113. 113.
    Carr BA, Ramakanth S, Dannan GA, Yost GS. Characterization of pulmonary cyp4b2, specific catalyst of methyl oxidation of 3-methylindole. Mol Pharmacol. 2003;63:1137–47.PubMedGoogle Scholar
  114. 114.
    Kartha JS, Yost GS. Mechanism-based inactivation of lung-selective cytochrome p450 cyp2f enzymes. Drug Metab Dispos. 2008;36:155–62.PubMedGoogle Scholar
  115. 115.
    Kaster JK, Yost GS. Production and characterization of specific antibodies: utilization to predict organ- and species-selective pneumotoxicity of 3-methylindole. Toxicol Appl Pharmacol. 1997;143:324–37.PubMedGoogle Scholar
  116. 116.
    Nichols WK, Mehta R, Skordos K, Mace K, Pfeifer AM, Carr BA, et al. 3-methylindole-induced toxicity to human bronchial epithelial cell lines. Toxicol Sci. 2003;71:229–36.PubMedGoogle Scholar
  117. 117.
    Nocerini MR, Carlson JR, Yost GS. Adducts of 3-methylindole and glutathione: species differences in organ-selective bioactivation. Toxicol Lett. 1985;28:79–87.PubMedGoogle Scholar
  118. 118.
    Yost GS, Kuntz DJ, McGill LD. Organ-selective switching of 3-methylindole toxicity by glutathione depletion. Toxicol Appl Pharmacol. 1990;103:40–51.PubMedGoogle Scholar
  119. 119.
    Teicher BA, Crawford JM, Holden SA, Lin Y, Cathcart KN, Luchette CA, et al. Glutathione monoethyl ester can selectively protect liver from high dose bcnu or cyclophosphamide. Cancer. 1988;62:1275–81.PubMedGoogle Scholar
  120. 120.
    Plopper CG, Suverkropp C, Morin D, Nishio S, Buckpitt A. Relationship of cytochrome p-450 activity to clara cell cytotoxicity. I. Histopathologic comparison of the respiratory tract of mice, rats and hamsters after parenteral administration of naphthalene. J Pharmacol Exp Ther. 1992;261:353–63.PubMedGoogle Scholar
  121. 121.
    Rasmussen RE, Do DH, Kim TS, Dearden LC. Comparative cytotoxicity of naphthalene and its monomethyl- and mononitro-derivatives in the mouse lung. J Appl Toxicol. 1986;6:13–20.PubMedGoogle Scholar
  122. 122.
    Bolton JL, Thompson JA, Allentoff AJ, Miley FB, Malkinson AM. Metabolic activation of butylated hydroxytoluene by mouse bronchiolar clara cells. Toxicol Appl Pharmacol. 1993;123:43–9.PubMedGoogle Scholar
  123. 123.
    Kehrer JP, DiGiovanni J. Comparison of lung injury induced in 4 strains of mice by butylated hydroxytoluene. Toxicol Lett. 1990;52:55–61.PubMedGoogle Scholar
  124. 124.
    Yamamoto K, Kato S, Tajima K, Mizutani T. Electronic and structural requirements for metabolic activation of butylated hydroxytoluene analogs to their quinone methides, intermediates responsible for lung toxicity in mice. Biol Pharm Bull. 1997;20:571–3.PubMedGoogle Scholar
  125. 125.
    Hanzlik RP, Stitt R, Traiger GJ. Toxic effects of methylcyclopentadienyl manganese tricarbonyl (mmt) in rats: role of metabolism. Toxicol Appl Pharmacol. 1980;56:353–60.PubMedGoogle Scholar
  126. 126.
    Kacew S, Parulekar MR, Narbaitz R, Ruddick JA, Villeneuve DC. Modification by phenobarbital of chlorphentermine-induced changes in lung morphology and drug-metabolizing enzymes in newborn rats. J Toxicol Environ Health. 1981;8:873–84.PubMedGoogle Scholar
  127. 127.
    Eltom SE, Babish JG, Schwark WS. The postnatal development of drug-metabolizing enzymes in hepatic, pulmonary and renal tissues of the goat. J Vet Pharmacol Ther. 1993;16: 152–63.PubMedGoogle Scholar
  128. 128.
    Eltom SE, Schwark WS. Cyp1a1 and cyp1b1, two hydrocarbon-inducible cytochromes p450, are constitutively expressed in neonate and adult goat liver, lung and kidney. Pharmacol Toxicol. 1999;85:65–73.PubMedGoogle Scholar
  129. 129.
    Fanucchi MV, Murphy ME, Buckpitt AR, Philpot RM, Plopper CG. Pulmonary cytochrome p450 monooxygenase and clara cell differentiation in mice. Am J Resp Cell Molec Biol. 1997;17:302–14.Google Scholar
  130. 130.
    Fouts JR, Devereux TR. Developmental aspects of hepatic and extrahepatic drug-metabolizing enzyme systems: microsomal enzymes and components in rabbit liver and lung during the first month of life. J Pharmacol Exp Ther. 1972;183:458–68.PubMedGoogle Scholar
  131. 131.
    Ji CM, Plopper CG, Witschi HP, Pinkerton KE. Exposure to sidestream cigarette smoke alters bronchiolar epithelial cell differentiation in the postnatal rat lung. Am J Respir Cell Mol Biol. 1994;11:312–20.PubMedGoogle Scholar
  132. 132.
    Ji CM, Cardoso WV, Gebremichael A, Philpot RM, Buckpitt AR, Plopper CG, et al. Pulmonary cytochrome p-450 monooxygenase system and clara cell differentiation in rats. Am J Physiol. 1995;269:L394–402.PubMedGoogle Scholar
  133. 133.
    Parandoosh Z, Franklin MR. Developmental changes in rabbit pulmonary cytochrome p-450 subpopulations. Life Sci. 1983;33:1255–60.PubMedGoogle Scholar
  134. 134.
    Simmons DL, Kasper CB. Quantitation of mrnas specific for the mixed-function oxidase system in rat liver and extrahepatic tissues during development. Arch Biochem Biophys. 1989;271:10–20.PubMedGoogle Scholar
  135. 135.
    Strum JM, Ito T, Philpot RM, DeSanti AM, McDowell EM. The immunocytochemical detection of cytochrome p-450 monooxygenase in the lungs of fetal, neonatal, and adult hamsters. Am J Respir Cell Mol Biol. 1990;2:493–501.PubMedGoogle Scholar
  136. 136.
    Plopper CG, Weir AJ, Morin D, Chang A, Philpot RM, Buckpitt AR. Postnatal changes in the expression and distribution of pulmonary cytochrome p450 monooxygenases during clara cell differentiation in rabbits. Mol Pharmacol. 1993;44:51–61.PubMedGoogle Scholar
  137. 137.
    Gebremichael A, Chang AM, Buckpitt AR, Plopper CG, Pinkerton KE. Postnatal development of cytochrome p4501a1 and 2b1 in rat lung and liver: effect of aged and diluted sidestream cigarette smoke. Toxicol Appl Pharmacol. 1995;135:246–53.PubMedGoogle Scholar
  138. 138.
    Fanucchi MV, Day KC, Clay CC, Plopper CG. Increased vulnerability of neonatal rats and mice to 1-nitronaphthalene-induced pulmonary injury. Toxicol Appl Pharmacol. 2004;201:53–65.PubMedGoogle Scholar
  139. 139.
    Larsen-Su S, Krueger SK, Yueh MF, Lee MY, Shehin SE, Hines RN, et al. Flavin-containing monooxygenase isoform 2: developmental expression in fetal and neonatal rabbit lung. J Biochem Mol Toxicol. 1999;13:187–93.PubMedGoogle Scholar
  140. 140.
    Stevens JC. New perspectives on the impact of cytochrome p450 3a expression for pediatric pharmacology. Drug Discov Today. 2006;11:440–5.PubMedGoogle Scholar
  141. 141.
    Day KC, Plopper CG, Fanucchi MV. Age-specific pulmonary cytochrome p-450 3a1 expression in postnatal and adult rats. Am J Physiol Lung Cell Mol Physiol. 2006;291:L75–83.PubMedGoogle Scholar
  142. 142.
    Hayes JD, Flanagan JU, Jowsey IR. Glutathione transferases. Ann Rev Pharmacol Toxicol. 2005;45:51–88.Google Scholar
  143. 143.
    Landi S. Mammalian class theta gst and differential susceptibility to carcinogens: a review. Mutat Res. 2000;463:247–83.PubMedGoogle Scholar
  144. 144.
    Mannervik B. The isoenzymes of glutathione transferase. Adv Enzymol Relat Areas Mol Biol. 1985;57:357–417.PubMedGoogle Scholar
  145. 145.
    Mannervik B, Danielson UH. Glutathione transferases–structure and catalytic activity. Crc Crit Rev Biochem. 1988;23:283–337.PubMedGoogle Scholar
  146. 146.
    Mannervik B, Board PG, Hayes JD, Listowsky I, Pearson WR. Nomenclature for mammalian soluble glutathione transferases. Methods Enzymol. 2005;401:1–8.PubMedGoogle Scholar
  147. 147.
    Buetler TM, Eaton DL. Complementary dna cloning, messenger rna expression, and induction of alpha-class glutathione s-transferases in mouse tissues. Cancer Res. 1992;52:314–8.PubMedGoogle Scholar
  148. 148.
    Fanucchi MV, Buckpitt AR, Murphy ME, Storms DH, Hammock BD, Plopper CG. Development of phase ii xenobiotic metabolizing enzymes in differentiating murine clara cells. Toxicol Appl Pharmacol. 2000;168:253–67.PubMedGoogle Scholar
  149. 149.
    James MO, Foureman GL, Law FC, Bend JR. The perinatal development of epoxide-metabolizing enzyme activities in liver and extrahepatic organs of guinea pig and rabbit. Drug Metab Dispos. 1977;5:19–28.PubMedGoogle Scholar
  150. 150.
    Beckett GJ, Howie AF, Hume R, Matharoo B, Hiley C, Jones P, et al. Human glutathione s-transferases: radioimmunoassay studies on the expression of alpha-, mu- and pi-class isoenzymes in developing lung and kidney. Biochim Biophys Acta. 1990;1036:176–82.PubMedGoogle Scholar
  151. 151.
    Cossar D, Bell J, Strange R, Jones M, Sandison A, Hume R. The alpha and pi isoenzymes of glutathione s-transferase in human fetal lung: in utero ontogeny compared with differentiation in lung organ culture. Biochim Biophys Acta. 1990;1037:221–6.PubMedGoogle Scholar
  152. 152.
    Fryer AA, Hume R, Strange RC. The development of glutathione s-transferase and glutathione peroxidase activities in human lung. Biochim Biophys Acta. 1986;883:448–53.PubMedGoogle Scholar
  153. 153.
    Pacifici GM, Franchi M, Colizzi C, Giuliani L, Rane A. Glutathione s-transferase in humans: development and tissue distribution. Arch Toxicol. 1988;61:265–9.PubMedGoogle Scholar
  154. 154.
    Omiecinski CJ, Aicher L, Swenson L. Developmental expression of human microsomal epoxide hydrolase. J Pharmacol Exp Ther. 1994;269:417–23.PubMedGoogle Scholar
  155. 155.
    Pacifici GM, Rane A. Metabolism of styrene oxide in different human fetal tissues. Drug Metab Dispos. 1982;10:302–5.PubMedGoogle Scholar
  156. 156.
    Lakritz J, Winder BS, Noorouz-Zadeh J, Huang TL, Buckpitt AR, Hammock BD, et al. Hepatic and pulmonary enzyme activities in horses. Am J Vet Res. 2000;61:152–7.PubMedGoogle Scholar
  157. 157.
    Datta K, Roy SK, Mitra AK, Kulkarni AP. Glutathione s-transferase mediated detoxification and bioactivation of xenobiotics during early human pregnancy. Early Hum Dev. 1994;37:167–74.PubMedGoogle Scholar
  158. 158.
    Strange RC, Davis BA, Faulder CG, Cotton W, Bain AD, Hopkinson DA, et al. The human glutathione s-transferases: developmental aspects of the gst1, gst2, and gst3 loci. Biochem Genet. 1985;23:1011–28.PubMedGoogle Scholar
  159. 159.
    Pacifici GM, Franchi M, Bencini C, Repetti F, Di Lascio N, Muraro GB. Tissue distribution of drug-metabolizing enzymes in humans. Xenobiotica. 1988;18:849–56.PubMedGoogle Scholar
  160. 160.
    Wixtrom RN, Hammock BD. Membrane-bound and soluble-fraction epoxide hydrolases: methodological aspects. In: Zakim D, Vessey DA, editors. Biochemical pharmacology and toxicology. New York: Wiley; 1985. p. 3–93.Google Scholar
  161. 161.
    Hassett C, Turnblom SM, DeAngeles A, Omiecinski CJ. Rabbit microsomal epoxide hydrolase: isolation and characterization of the xenobiotic metabolizing enzyme cdna. Arch Biochem Biophys. 1989;271:380–9.PubMedGoogle Scholar
  162. 162.
    de Waziers I, Cugnenc PH, Yang CS, Leroux JP, Beaune PH. Cytochrome p 450 isoenzymes, epoxide hydrolase and glutathione transferases in rat and human hepatic and extrahepatic tissues. J Pharmacol Exp Ther. 1990;253:387–94.PubMedGoogle Scholar
  163. 163.
    Waechter F, Bentley P, Bieri F, Muakkassah-Kelly S, Staubli W, Villermain M. Organ distribution of epoxide hydrolases in cytosolic and microsomal fractions of normal and nafenopin-treated male dba/2 mice. Biochem Pharmacol. 1988;37:3897–903.PubMedGoogle Scholar
  164. 164.
    Pacifici GM, Temellini A, Giuliani L, Rane A, Thomas H, Oesch F. Cytosolic epoxide hydrolase in humans: development and tissue distribution. Arch Toxicol. 1988;62:254–7.PubMedGoogle Scholar
  165. 165.
    Bond JA, Harkema JR, Russell VI. Regional distribution of xenobiotic metabolizing enzymes in respiratory airways of dogs. Drug Metab Dispos. 1988;16:116–24.PubMedGoogle Scholar
  166. 166.
    Kaur S, Gill SS. Age-related changes in the activities of epoxide hydrolases in different tissues of mice. Drug Metab Dispos. 1985;13:711–5.PubMedGoogle Scholar
  167. 167.
    Statham CN, Dutcher JS, Kim SH, Boyd MR. Ipomeanol 4-glucuronide, a major urinary metabolite of 4-ipomeanol in the rat. Drug Metab Dispos. 1982;10:264–7.PubMedGoogle Scholar
  168. 168.
    Baron J, Voigt JM. Localization, distribution, and induction of xenobiotic-metabolizing enzymes and aryl hydrocarbon hydroxylase activity within lung. Pharmacol Ther. 1990;47: 419–45.PubMedGoogle Scholar
  169. 169.
    Kawalek JC, el Said KR. Maturational development of drug-metabolizing enzymes in dogs. Am J Vet Res. 1990;51:1742–5.PubMedGoogle Scholar
  170. 170.
    Kawalek JC, el Said KR. Maturational development of drug-metabolizing enzymes in sheep. Am J Vet Res. 1990;51:1736–41.PubMedGoogle Scholar
  171. 171.
    Pacifici GM, Kubrich M, Giuliani L, de Vries M, Rane A. Sulphation and glucuronidation of ritodrine in human foetal and adult tissues. Eur J Clin Pharmacol. 1993;44:259–64.PubMedGoogle Scholar
  172. 172.
    Hume R, Barker EV, Coughtrie MW. Differential expression and immunohistochemical localisation of the phenol and hydroxysteroid sulphotransferase enzyme families in the developing lung. Histochem Cell Biol. 1996;105:147–52.PubMedGoogle Scholar
  173. 173.
    Cashman JR. Human flavin-containing monooxygenase: substrate specificity and role in drug metabolism. Curr Drug Metab. 2000;1:181–91.PubMedGoogle Scholar
  174. 174.
    Ziegler DM. Flavin-containing monooxygenases: enzymes adapted for multisubstrate specificity. Trends Pharmacol Sci. 1990;11:321–4.PubMedGoogle Scholar
  175. 175.
    Coughtrie MW, Sharp S, Maxwell K, Innes NP. Biology and function of the reversible sulfation pathway catalysed by human sulfotransferases and sulfatases. Chem Biol Interact. 1998;109:3–27.PubMedGoogle Scholar
  176. 176.
    Falany CN. Enzymology of human cytosolic sulfotransferases. Faseb J. 1997;11:206–16.PubMedGoogle Scholar
  177. 177.
    Glatt H, Boeing H, Engelke CE, Ma L, Kuhlow A, Pabel U, et al. Human cytosolic sulphotransferases: genetics, characteristics, toxicological aspects. Mutat Res. 2001;482:27–40.PubMedGoogle Scholar
  178. 178.
    Richard K, Hume R, Kaptein E, Stanley EL, Visser TJ, Coughtrie MW. Sulfation of thyroid hormone and dopamine during human development: ontogeny of phenol sulfotransferases and arylsulfatase in liver, lung, and brain. J Clin Endocrinol Metab. 2001;86:2734–42.PubMedGoogle Scholar
  179. 179.
    Ji CM, Royce FH, Truong U, Plopper CG, Singh G, Pinkerton KE. Maternal exposure to environmental tobacco smoke alters clara cell secretory protein expression in fetal rat lung. Am J Physiol. 1998;275:L870–6.PubMedGoogle Scholar
  180. 180.
    Lee CZ, Royce FH, Denison MS, Pinkerton KE. Effect of in utero and postnatal exposure to environmental tobacco smoke on the developmental expression of pulmonary cytochrome p450 monooxygenases. J Biochem Mol Toxicol. 2000;14:121–30.PubMedGoogle Scholar
  181. 181.
    Gamieldien K, Maritz G. Postnatal expression of cytochrome p450 1a1, 2a3, and 2b1 mrna in neonatal rat lung: influence of maternal nicotine exposure. Exp Lung Res. 2004;30: 121–33.PubMedGoogle Scholar
  182. 182.
    Sindhu RK, Rasmussen RE, Kikkawa Y. Effect of environmental tobacco smoke on the metabolism of (-)-trans-benzo[a]pyrene-7,8-dihydrodiol in juvenile ferret lung and liver. J Toxicol Environ Health. 1995;45:453–64.PubMedGoogle Scholar
  183. 183.
    Uejima Y, Fukuchi Y, Nagase T, Matsuse T, Yamaoka M, Orimo H. Influences of tobacco smoke and vitamin e depletion on the distal lung of weanling rats. Exp Lung Res. 1995;21: 631–42.PubMedGoogle Scholar
  184. 184.
    Mutoh T, Bonham AC, Kott KS, Joad JP. Chronic exposure to sidestream tobacco smoke augments lung c-fiber responsiveness in young guinea pigs. J Appl Physiol. 1999;87:757–68.PubMedGoogle Scholar
  185. 185.
    Bonham AC, Chen CY, Mutoh T, Joad JP. Lung c-fiber cns reflex: role in the respiratory consequences of extended environmental tobacco smoke exposure in young guinea pigs. Environ Health Perspect. 2001;109 Suppl 4:573–8.PubMedCentralPubMedGoogle Scholar
  186. 186.
    Mutoh T, Joad JP, Bonham AC. Chronic passive cigarette smoke exposure augments bronchopulmonary c-fibre inputs to nucleus tractus solitarii neurones and reflex output in young guinea-pigs. J Physiol. 2000;523(Pt 1):223–33.PubMedCentralPubMedGoogle Scholar
  187. 187.
    Joad JP, Pinkerton KE, Bric JM. Effects of sidestream smoke exposure and age on pulmonary function and airway reactivity in developing rats. Pediatr Pulmonol. 1993;16:281–8.PubMedGoogle Scholar
  188. 188.
    Joad JP, Bric JM, Peake JL, Pinkerton KE. Perinatal exposure to aged and diluted sidestream cigarette smoke produces airway hyperresponsiveness in older rats. Toxicol Appl Pharmacol. 1999;155:253–60.PubMedGoogle Scholar
  189. 189.
    Slotkin TA, Pinkerton KE, Seidler FJ. Perinatal exposure to environmental tobacco smoke alters cell signaling in a primate model: autonomic receptors and the control of adenylyl cyclase activity in heart and lung. Brain Res Dev Brain Res. 2000;124:53–8.PubMedGoogle Scholar
  190. 190.
    Wang L, Joad JP, Zhong C, Pinkerton KE. Effects of environmental tobacco smoke exposure on pulmonary immune response in infant monkeys. J Allergy Clin Immunol. 2008;122(2):400–6, 406.e1–5, Corrected Proof.PubMedGoogle Scholar
  191. 191.
    Rouet P, Dansette P, Frayssinet C. Ontogeny of benzo(a)pyrene hydroxylase, epoxide hydrolase and glutathione-S-transferase in the brain, lung and liver of c57bl/6 mice. Dev Pharmacol Ther. 1984;7:245–58.PubMedGoogle Scholar
  192. 192.
    Penn AL, Rouse RL, Horohov DW, Kearney MT, Paulsen DB, Lomax L. In utero exposure to environmental tobacco smoke potentiates adult responses to allergen in balb/c mice. Environ Health Perspect. 2007;115:548–55.PubMedCentralPubMedGoogle Scholar
  193. 193.
    Lannero E, Wickman M, Pershagen G, Nordvall L. Maternal smoking during pregnancy increases the risk of recurrent wheezing during the first years of life (bamse). Respir Res. 2006;7:3.PubMedCentralPubMedGoogle Scholar
  194. 194.
    Matulionis DH. Chronic cigarette smoke inhalation and aging in mice: 1. Morphologic and functional lung abnormalities. Exp Lung Res. 1984;7:237–56.PubMedGoogle Scholar
  195. 195.
    Teramoto S, Uejima Y, Oka T, Teramoto K, Matsuse T, Ouchi Y, et al. Effects of chronic cigarette smoke inhalation on the development of senile lung in senescence-accelerated mouse. Res Exp Med (Berl). 1997;197:1–11.Google Scholar
  196. 196.
    Uejima Y, Fukuchi Y, Nagase T, Matsuse T, Yamaoka M, Tabata R, et al. Influences of inhaled tobacco smoke on the senescence accelerated mouse (sam). Eur Respir J. 1990;3:1029–36.PubMedGoogle Scholar
  197. 197.
    Ulrich P, Cerami A. Protein glycation, diabetes, and aging. Recent Prog Horm Res. 2001;56:1–21.PubMedGoogle Scholar
  198. 198.
    Kerstjens HA, Rijcken B, Schouten JP, Postma DS. Decline of fev1 by age and smoking status: facts, figures, and fallacies. Thorax. 1997;52:820–7.PubMedCentralPubMedGoogle Scholar
  199. 199.
    Lange P, Groth S, Nyboe J, Mortensen J, Appleyard M, Jensen G, et al. Decline of the lung function related to the type of tobacco smoked and inhalation. Thorax. 1990;45:22–6.PubMedCentralPubMedGoogle Scholar
  200. 200.
    Gairola C, Aleem MI. Cigarette smoke: effect of aqueous and nonaqueous fractions on mitochondrial function. Nature. 1973;241:287–8.PubMedGoogle Scholar
  201. 201.
    Konga DB, Kim Y, Hong SC, Roh YM, Lee CM, Kim KY, et al. Oxidative stress and antioxidant defenses in asthmatic murine model exposed to printer emissions and environmental tobacco smoke. J Environ Pathol Toxicol Oncol. 2009;28:325–40.PubMedGoogle Scholar
  202. 202.
    Carter CA, Hamm JT. Multiplexed quantitative high content screening reveals that cigarette smoke condensate induces changes in cell structure and function through alterations in cell signaling pathways in human bronchial cells. Toxicology. 2009;261:89–102.PubMedGoogle Scholar
  203. 203.
    van der Toorn M, Rezayat D, Kauffman HF, Bakker SJ, Gans RO, Koeter GH, et al. Lipid-soluble components in cigarette smoke induce mitochondrial production of reactive oxygen species in lung epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2009;297: L109–14.PubMedCentralPubMedGoogle Scholar
  204. 204.
    Boyd MR, Reznik-Schuller HM. Metabolic basis for the pulmonary clara cell as a target for pulmonary carcinogenesis. Toxicol Pathol. 1984;12:56–61.PubMedGoogle Scholar
  205. 205.
    Buckpitt A, Buonarati M, Avey LB, Chang AM, Morin D, Plopper CG. Relationship of cytochrome p450 activity to clara cell cytotoxicity. Ii. Comparison of stereoselectivity of naphthalene epoxidation in lung and nasal mucosa of mouse, hamster, rat and rhesus monkey. J Pharmacol Exp Ther. 1992;261:364–72.PubMedGoogle Scholar
  206. 206.
    Ding X, Kaminsky LS. Human extrahepatic cytochromes p450: function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts. Annu Rev Pharmacol Toxicol. 2003;43:149–73.PubMedGoogle Scholar
  207. 207.
    Forkert PG, Birch DW. Pulmonary toxicity of trichloroethylene in mice. Covalent binding and morphological manifestations. Drug Metab Dispos. 1989;17:106–13.PubMedGoogle Scholar
  208. 208.
    Johnson DE, Riley MG, Cornish HH. Acute target organ toxicity of 1-nitronaphthalene in the rat. J Appl Toxicol. 1984;4:253–7.PubMedGoogle Scholar
  209. 209.
    O’Brien KA, Smith LL, Cohen GM. Differences in naphthalene-induced toxicity in the mouse and rat. Chem Biol Interact. 1985;55:109–22.PubMedGoogle Scholar
  210. 210.
    Ogawa T, Tsubakihara M, Ichikawa M, Kanisawa M. An autoradiographic study of the renewal of mouse bronchiolar epithelium following bromobenzene exposure. Toxicol Pathol. 1993;21:547–53.PubMedGoogle Scholar
  211. 211.
    Paige R, Wong V, Plopper C. Dose-related airway-selective epithelial toxicity of 1-nitronaphthalene in rats. Toxicol Appl Pharmacol. 1997;147:224–33.PubMedGoogle Scholar
  212. 212.
    Fanucchi MV, Buckpitt AR, Murphy ME, Plopper CG. Naphthalene cytotoxicity in the differentiating clara cells of neonatal mice. Toxicol Appl Pharmacol. 1997;144:96–104.PubMedGoogle Scholar
  213. 213.
    Plopper CG, Weir AJ, Nishio SJ, Chang A, Voit M, Philpot RM, et al. Elevated susceptibility to 4-ipomeanol cytotoxicity in immature clara cells of neonatal rabbits. J Pharmacol Exp Ther. 1994;269:867–80.PubMedGoogle Scholar
  214. 214.
    Smiley-Jewell SM, Liu FJ, Weir AJ, Plopper CG. Acute injury to differentiating clara cells in neonatal rabbits results in age-related failure of bronchiolar repair. Toxicol Pathol. 2000;28:267–76.PubMedGoogle Scholar
  215. 215.
    Faustman-Watts E, Giachelli C, Juchau M. Carbon monoxide inhibits monooxygenation by the conceptus and embryotoxic effects of proteratogens in vitro. Toxicol Appl Pharmacol. 1986;83:590–5.PubMedGoogle Scholar
  216. 216.
    Faustman-Watts E, Namkung M, Juchau M. Modulation of the embryotoxicity in vitro of reactive metabolites of 2-acetylaminofluorene by reduced glutathione and ascorbate and via sulfation. Toxicol Appl Pharmacol. 1986;86:400–10.PubMedGoogle Scholar
  217. 217.
    Filler R, Lew KJ. Developmental onset of mixed-function oxidase activity in preimplantation mouse embryos. Proc Natl Acad Sci U S A. 1981;78:6991–5.PubMedCentralPubMedGoogle Scholar
  218. 218.
    Galloway SM, Perry PE, Meneses J, Nebert DW, Pedersen RA. Cultured mouse embryos metabolize benzo[a]pyrene during early gestation: genetic differences detectable by sister chromatid exchange. Proc Natl Acad Sci U S A. 1980;77:3524–8.PubMedCentralPubMedGoogle Scholar
  219. 219.
    Juchau MR, Giachelli CM, Fantel AG, Greenaway JC, Shepard TH, Faustman-Watts EM. Effects of 3-methylcholanthrene and phenobarbital on the capacity of embryos to bioactivate teratogens during organogenesis. Toxicol Appl Pharmacol. 1985;80:137–46.PubMedGoogle Scholar
  220. 220.
    Juchau MR. Bioactivation in chemical teratogenesis. Annu Rev Pharmacol Toxicol. 1989;29:165–87.PubMedGoogle Scholar
  221. 221.
    Palmer KC. Clara cell adenomas of the mouse lung. Interaction with alveolar type 2 cells. Am J Pathol. 1985;120:455–63.PubMedCentralPubMedGoogle Scholar
  222. 222.
    Yang HY, Namkung MJ, Juchau MR. Immunodetection, immunoinhibition, immunoquantitation and biochemical analyses of cytochrome p-450ia1 in tissues of the ratoffceptus during the progression of organogenesis. Biochem Pharmacol. 1989;38:4027–36.PubMedGoogle Scholar
  223. 223.
    Eriksson C, Brittebo EB. Dichlobenil in the fetal and neonatal mouse olfactory mucosa. Toxicology. 1995;96:93–104.PubMedGoogle Scholar
  224. 224.
    Durham SK, Boyd MR, Castleman WL. Pulmonary endothelial and bronchiolar epithelial lesions induced by 4-ipomeanol in mice. Am J Pathol. 1985;118:66–75.PubMedCentralPubMedGoogle Scholar
  225. 225.
    Van Winkle LS, Buckpitt AR, Nishio SJ, Isaac JM, Plopper CG. Cellular response in naphthalene-induced clara cell injury and bronchiolar epithelial repair in mice. Am J Physiol. 1995;269:L800–18.PubMedGoogle Scholar
  226. 226.
    Van Winkle LS, Johnson ZA, Nishio SJ, Bronn CD, Plopper CG. Early events in naphthalene-induced acute clara cell toxicity - comparison of membrane permeability and ultrastructure. Am J Resp Cell Mol Biol. 1999;21:44–53.Google Scholar
  227. 227.
    Forkert PG, Dowsley TF, Lee RP, Hong JY, Ulreich JB. Differential formation of 1,1-dichloroethylene-metabolites in the lungs of adult and weanling male and female mice: correlation with severities of bronchiolar cytotoxicity. J Pharmacol Exp Ther. 1996;279:1484–90.PubMedGoogle Scholar
  228. 228.
    Drechsler-Parks DM, Horvath SM, Bedi JF. The “effective dose” concept in older adults exposed to ozone. Exp Gerontol. 1990;25:107–15.PubMedGoogle Scholar
  229. 229.
    Hoppe P, Praml G, Rabe G, Lindner J, Fruhmann G, Kessel R. Environmental ozone field study on pulmonary and subjective responses of assumed risk groups. Environ Res. 1995;71:109–21.PubMedGoogle Scholar
  230. 230.
    Man SFP, Hulbert WC. Pathophysiology and treatment of inhalation injuries. New York: Marcel Dekker, Inc.; 1988.Google Scholar
  231. 231.
    Frank L, Bucher JR, Roberts RJ. Oxygen toxicity in neonatal and adult animals of various species. Am Physiol Soc. 1978;45(5):699–704.Google Scholar
  232. 232.
    Hoffman M, Stevens JB, Autor AP. Adaptation to hyperoxia in the neonatal rat: kinetic parameters of the oxygen-mediated induction of lung superoxide dismutases, catalase and glutathione peroxidase. Toxicology. 1980;16:215–25.PubMedGoogle Scholar
  233. 233.
    Dennery PA, Rodgers PA, Lum MA, Jennings BC, Shokoohi V. Hyperoxic regulation of lung heme oxygenase in neonatal rats. Pediatr Res. 1996;40:815–21.PubMedGoogle Scholar
  234. 234.
    Kim HS, Kang SW, Rhee SG, Clerch LB. Rat lung peroxiredoxins i and ii are differentially regulated during development and by hyperoxia. Am J Physiol Lung Cell Mol Physiol. 2001;280:L1212–7.PubMedGoogle Scholar
  235. 235.
    Yang G, Madan A, Dennery PA. Maturational differences in hyperoxic ap-1 activation in rat lung. Am J Physiol Lung Cell Mol Physiol. 2000;278:L393–8.PubMedGoogle Scholar
  236. 236.
    Bartlett DJ, Faulkner II CS, Cook K. Effect of chronic ozone exposure on lung elasticity in young rats. JApplPhysiol. 1974;37(1):92–6.Google Scholar
  237. 237.
    Bonuccelli CM, Permutt S, Sylvester JT. Developmental differences in catalase activity and hypoxic-hyperoxic effects on fluid balance in isolated lamb lungs. Pediatr Res. 1993;33: 519–26.PubMedGoogle Scholar
  238. 238.
    Bucher JR, Roberts RJ. The development of the newborn rat lung in hyperoxia: a dose-response study of lung growth, maturation, and changes in antioxidant enzyme activities. Pediatr Res. 1981;15:999–1008.PubMedGoogle Scholar
  239. 239.
    Kennedy KA, Lane NL. Effect of in vivo hyperoxia on the glutathione system in neonatal rat lung. Exp Lung Res. 1994;20:73–83.PubMedGoogle Scholar
  240. 240.
    Langley SC, Kelly FJ. Depletion of pulmonary glutathione using diethylmaleic acid accelerates the development of oxygen-induced lung injury in term and preterm guinea-pig neonates. J Pharm Pharmacol. 1993;46:98–102.Google Scholar
  241. 241.
    Chessex P, Lavoie JC, Laborie S, Vallee J. Survival of guinea pig pups in hyperoxia is improved by enhanced nutritional substrate availability for glutathione production. Pediatr Res. 1999;46:305–10.PubMedGoogle Scholar
  242. 242.
    Frank L, Groseclose E. Oxygen toxicity in newborn rats: the adverse effects of undernutrition. Am Physiol Soc. 1982;53(5):1248–55.Google Scholar
  243. 243.
    Frank L. Prenatal dexamethasone treatment improves survival of newborn rats during prolonged high o2 exposure. Ped Res. 1992;32:215–21.Google Scholar
  244. 244.
    Sosenko IR, Chen Y, Price LT, Frank L. Failure of premature rabbits to increase lung antioxidant enzyme activities after hyperoxic exposure: antioxidant enzyme gene expression and pharmacologic intervention with endotoxin and dexamethasone. Ped Res. 1995;37:469–75.Google Scholar
  245. 245.
    Barnard JA, Lyons RM, Moses HL. The cell biology of transforming growth factor b. Biochim Biophys Acta Rev Cancer. 1990;1032:79–87.Google Scholar
  246. 246.
    Bartlett D. Postnatal growth of the mammalian lung: influence of low and high oxygen tensions. Respir Physiol. 1970;9:58–64.PubMedGoogle Scholar
  247. 247.
    Burri PH, Weibel ER. Ultrastructure and morphometry of the developing lung. In: Hodson WA, editor. Development of the lung, vol. 6. New York: Marcel Dekker; 1977. p. 215–68.Google Scholar
  248. 248.
    Koppel R, Han RNN, Cox D, Tanswell AK, Rabinovitch M. A1-antitrypsin protects neonatal rats from pulmonary vascular and parenchymal effects of oxygen toxicity. Ped Res. 1994;36:763–70.Google Scholar
  249. 249.
    Massaro GD, Olivier J, Massaro D. Brief perinatal hypoxia impairs postnatal development of the bronchiolar epithelium. Am J Physiol. 1989;257:L80–5.PubMedGoogle Scholar
  250. 250.
    Ratner V, Starkov A, Matsiukevich D, Polin RA, Ten VS. Mitochondrial dysfunction contributes to alveolar developmental arrest in hyperoxia-exposed mice. Am J Respir Cell Mol Biol. 2009;40:511–8.PubMedCentralPubMedGoogle Scholar
  251. 251.
    Veness-Meehan KA, Bottone Jr FG, Stiles AD. Effects of retinoic acid on airspace development and lung collagen in hyperoxia-exposed newborn rats. Pediatr Res. 2000;48:434–44.PubMedGoogle Scholar
  252. 252.
    Veness-Meehan KA, Pierce RA, Moats-Staats BM, Stiles AD. Retinoic acid attenuates o2-induced inhibition of lung septation. Am J Physiol Lung Cell Mol Physiol. 2002;283: L971–80.PubMedGoogle Scholar
  253. 253.
    Chen C, Wang LF, Chou H, Lang YD, Lai YP. Up-regulation of connective tissue growth factor in hyperoxia-induced lung fibrosis. Pediatr Res. 2007;62:128–33.PubMedGoogle Scholar
  254. 254.
    Keeney SE, Mathews MJ, Haque AK, Schmalstieg FC. Comparison of pulmonary neutrophils in the adult and neonatal rat after hyperoxia. Pediatr Res. 1995;38:857–63.PubMedGoogle Scholar
  255. 255.
    Auten Jr RL, Mason SN, Tanaka DT, Welty-Wolf K, Whorton MH. Anti-neutrophil chemokine preserves alveolar development in hyperoxia-exposed newborn rats. Am J Physiol Lung Cell Mol Physiol. 2001;281:L336–44.PubMedGoogle Scholar
  256. 256.
    Auten RL, Whorton MH, Nicholas MS. Blocking neutrophil influx reduces dna damage in hyperoxia-exposed newborn rat lung. Am J Respir Cell Mol Biol. 2002;26:391–7.PubMedGoogle Scholar
  257. 257.
    Manji JS, O’Kelly CJ, Leung WI, Olson DM. Timing of hyperoxic exposure during alveolarization influences damage mediated by leukotrienes. Am J Physiol Lung Cell Mol Physiol. 2001;281:L799–806.PubMedGoogle Scholar
  258. 258.
    McGrath-Morrow SA, Stahl J. Apoptosis in neonatal murine lung exposed to hyperoxia. Am J Respir Cell Mol Biol. 2001;25:150–5.PubMedGoogle Scholar
  259. 259.
    Massaro GD, McCoy L, Massaro D. Hyperoxia reversibly suppresses development of bronchiolar epithelium. Am J Physiol. 1986;251:R1045–50.PubMedGoogle Scholar
  260. 260.
    Klimova TA, Bell EL, Shroff EH, Weinberg FD, Snyder CM, Dimri GP, et al. Hyperoxia-induced premature senescence requires p53 and prb, but not mitochondrial matrix ros. FASEB J. 2009;23:783–94.PubMedCentralPubMedGoogle Scholar
  261. 261.
    Barry BE, Miller FJ, Crapo JD. Effects of inhalation of 0.12 and 0.25 parts per million ozone on the proximal alveolar region of juvenile and adult rats. Lab Invest J Tech Methods Pathol. 1985;53:692–704.Google Scholar
  262. 262.
    Elsayed NM, Mustafa MG, Postlethwait EM. Age-dependent pulmonary response of rats to ozone exposure. J Toxicol Environ Health. 1982;9:835–48.PubMedGoogle Scholar
  263. 263.
    Raub JA, Mercer RR, Kavlock RJ. Effects of prenatal nitrofen exposure on postnatal lung function in the rat. Toxicol Appl Pharmacol. 1983;94:119–34.Google Scholar
  264. 264.
    Stephens RJ, Sloan MF, Groth DG, Negi DS, Lunan KD. Cytologic responses of postnatal rat lungs to o3 or no2 exposure. Am J Pathol. 1978;93:183–200.PubMedCentralPubMedGoogle Scholar
  265. 265.
    Tyson CA, Lunan KD, Stephens RJ. Age-related differences in gsh-shuttle enzymes in no2- or o3-exposed rat lungs. Arch Environ Health. 1982;37:167–76.PubMedGoogle Scholar
  266. 266.
    Stiles J, Tyler WS. Age-related morphometric differences in responses of rat lungs to ozone. Toxicol Appl Pharmacol. 1988;92:274–85.PubMedGoogle Scholar
  267. 267.
    Tyler WS, Tyler NK, Magliano DJ, Hinds DM, Tarkington B, Julian MD, et al. Effects of ozone inhalation on lungs of juvenile monkeys. Morphometry after a 12 month exposure and following a 6 month post-exposure. In: Berglund RL, Lawson DR, McKee DJ, editors. Tropospheric ozone and the environment. Pittsburg: Air & Waste Management Association; 1991. p. 152–9.Google Scholar
  268. 268.
    Mariassy AT, Sielczak MW, McCray MN, Abraham WM, Wanner A. Effects of ozone on lamb tracheal mucosa. Quantitative glycoconjugate histochemistry. Am J Pathol. 1989;135:871–9.PubMedCentralPubMedGoogle Scholar
  269. 269.
    Fanucchi MV, Plopper CG, Evans MJ, Hyde DM, Van Winkle LS, Gershwin LJ, et al. Cyclic exposure to ozone alters distal airway development in infant rhesus monkeys. Am J Physiol Lung Cell Mol Physiol. 2006;291:L644–50.PubMedGoogle Scholar
  270. 270.
    Kajekar R, Pieczarka EM, Smiley-Jewell SM, Schelegle ES, Fanucchi MV, Plopper CG. Early postnatal exposure to allergen and ozone leads to hyperinnervation of the pulmonary epithelium. Resp Physiol Neurobiol. 2007;155:55–63.Google Scholar
  271. 271.
    Evans MJ, Fanucchi MV, Baker GL, Van Winkle LS, Pantle LM, Nishio SJ, et al. Atypical development of the tracheal basement membrane zone of infant rhesus monkeys exposed to ozone and allergen. Am J Physiol Lung Cell Mol Physiol. 2003;285:L931–9.PubMedGoogle Scholar
  272. 272.
    Evans MJ, Van Winkle LS, Fanucchi MV, Plopper CG. The attenuated fibroblast sheath of the respiratory tract epithelial- mesenchymal trophic unit. Am J Respir Cell Mol Biol. 1999;21: 655–7.PubMedGoogle Scholar
  273. 273.
    Iozzo RV. Matrix proteoglycans: from molecular design to cellular function. Annu Rev Biochem. 1998;67:609–52.PubMedGoogle Scholar
  274. 274.
    Evans MJ, Van Winkle LS, Fanucchi MV, Baker GL, Murphy AE, Nishio SJ, et al. Fibroblast growth factor-2 in remodeling of the developing basement membrane zone in the trachea of infant rhesus monkeys sensitized and challenged with allergen. Lab Invest J Tech Methods Pathol. 2002;82:1747–54.Google Scholar
  275. 275.
    Jiang X, Couchman JR. Perlecan and tumor angiogenesis. J Histochem Cytochem. 2003;51: 1393–410.PubMedCentralPubMedGoogle Scholar
  276. 276.
    Avol EL, Gauderman WJ, Tan SM, London SJ, Peters JM. Respiratory effects of relocating to areas of differing air pollution levels. Am J Respir Crit Care Med. 2001;164:2067–72.PubMedGoogle Scholar
  277. 277.
    Gauderman WJ, McConnell R, Gilliland F, London S, Thomas D, Avol E, et al. Association between air pollution and lung function growth in southern california children. Am J Respir Crit Care Med. 2000;162:1383–90.PubMedGoogle Scholar
  278. 278.
    Peters JM, Avol E, Gauderman WJ, Linn WS, Navidi W, London SJ, et al. A study of twelve southern california communities with differing levels and types of air pollution. Ii. Effects on pulmonary function. Am J Respir Crit Care Med. 1999;159:768–75.PubMedGoogle Scholar
  279. 279.
    Peters JM, Avol E, Navidi W, London SJ, Gauderman WJ, Lurmann F, et al. A study of twelve southern california communities with differing levels and types of air pollution. I. Prevalence of respiratory morbidity. Am J Respir Crit Care Med. 1999;159:760–7.PubMedGoogle Scholar
  280. 280.
    Calderon-Garciduenas L, Mora-Tiscareno A, Chung CJ, Valencia G, Fordham LA, Garcia R, et al. Exposure to air pollution is associated with lung hyperinflation in healthy children and adolescents in southwest mexico city: a pilot study. Inhal Toxicol. 2000;12:537–61.PubMedGoogle Scholar
  281. 281.
    Calderon-Garciduenas L, Mora-Tiscareno A, Fordham LA, Valencia-Salazar G, Chung CJ, Rodriguez-Alcaraz A, et al. Respiratory damage in children exposed to urban pollution. Pediatr Pulmonol. 2003;36:148–61.PubMedGoogle Scholar
  282. 282.
    Calderon-Garciduenas L, Mora-Tiscareno A, Fordham LA, Chung CJ, Valencia-Salazar G, Flores-Gomez S, et al. Lung radiology and pulmonary function of children chronically exposed to air pollution. Environ Health Perspect. 2006;114:1432–7.PubMedCentralPubMedGoogle Scholar
  283. 283.
    Shore SA, Abraham JH, Schwartzman IN, Murthy GG, Laporte JD. Ventilatory responses to ozone are reduced in immature rats. J Appl Physiol. 2000;88:2023–30.PubMedGoogle Scholar
  284. 284.
    Gunnison AF, Finkelstein I, Weideman P, Su WY, Sobo M, Schlesinger RB. Age-dependent effect of ozone on pulmonary eicosanoid metabolism in rabbits and rats. Fundam Appl Toxicol. 1990;15:779–90.PubMedGoogle Scholar
  285. 285.
    Gunnison AF, Weideman PA, Sobo M, Koenig KL, Chen LC. Age-dependence of responses to acute ozone exposure in rats. Fundam Appl Toxicol. 1992;18:360–9.PubMedGoogle Scholar
  286. 286.
    Bae HJ, Park J. Health benefits of improving air quality in the rapidly aging korean society. Sci Total Environ. 2009;407:5971–7.PubMedGoogle Scholar
  287. 287.
    de Almeida SP, Casimiro E, Calheiros J. Short-term association between exposure to ozone and mortality in oporto, portugal. Environ Res. 2011;111:406–10.PubMedGoogle Scholar
  288. 288.
    Seal Jr E, McDonnell WF, House DE. Effects of age, socioeconomic status, and menstrual cycle on pulmonary response to ozone. Arch Environ Health. 1996;51:132–7.PubMedGoogle Scholar
  289. 289.
    van Bree L, Marra M, van Scheindelen HJ, Fischer PH, de Loos S, Buringh E, et al. Dose-effect models for ozone exposure: tool for quantitative risk estimation. Toxicol Lett. 1995;82–83:317–21.PubMedGoogle Scholar
  290. 290.
    Vincent R, Adamson IYR. Cellular kinetics in the lungs of aging fischer-344 rats after acute exposure to ozone. Am J Pathol. 1995;146:1008–16.PubMedCentralPubMedGoogle Scholar
  291. 291.
    Harman AW, McKenna M, Adamson GM. Postnatal development of enzyme activities associated with protection against oxidative stress in the mouse. Biol Neonate. 1990;57:187–93.PubMedGoogle Scholar
  292. 292.
    Gardlik S, Gasser R, Philpot RM, Serabjit-Singh CJ. The major alpha-class glutathione s-transferases of rabbit lung and liver. Primary sequences, expression, and regulation. J Biol Chem. 1991;266:19681–87.PubMedGoogle Scholar
  293. 293.
    Serabjit-Singh CJ, Bend JR. Purification and biochemical characterization of the rabbit pulmonary glutathione s-transferase: Stereoselectivity and activity toward pyrene 4,5-oxide. Arch Biochem Biophys. 1988;267:184–94.PubMedGoogle Scholar
  294. 294.
    Pacifici GM, Temellini A, Giuliani L, Rane A, Thomas H, Oesch F. Cytosolic epoxide hydrolase in humans: Development and tissue distribution. Arch Toxicol. 1988;62:254–57.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Department of MedicalCystic Fibrosis FoundationBethesdaUSA
  2. 2.Department of Environmental Health SciencesUniversity of Alabama at BirminghamBirminghamUSA

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