Porphyrin Metabolism as Indicator of Metal Exposure and Toxicity

  • J. S. Woods
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 115)

Abstract

Numerous studies during the past several decades have demonstrated that porphyrins and other constituents of the heme biosynthetic pathway might serve as sensitive and specific biomarkers of toxic metal exposures in human subjects. Porphyrins (in the reduced form, porphyrinogens) are formed as intermediates of heme biosynthesis in essentially all eukaryotic tissues and are readily measured following extraction in the oxidized form (porphyrins) in blood cells, urine, feces, and other accessible tissues. The utility of porphyrins as biomarkers of metal exposures is based largely on the properties of metals to selectively alter porphyrinogen metabolism in target tissues by mechanisms which lead to metal-specific changes in urinary porphyrin excretion patterns. Of particular importance with respect to the utility of porphyrins as biomarkers of metal effects in target tissues is the property of some specific metals, not only to impair porphyrin(ogen) metabolism, but also to facilitate the oxidation of reduced porphyrins which subsequently accumulate in tissue cells. Evidence indicates that the pro-oxidant action of metals which promotes porphyrinogen oxidation may also underlie the oxidation of other cellular constituents, such as lipids and proteins, a postulated cause of cell injury. Hence, a common mechanistic etiology underlying the porphyrinogenic and tissue-damaging properties of metals provides the rationale for use of porphyrin measurements as an indicator of metal exposure as well as potential toxicity.

Keywords

Toxicity Cadmium GaAs Gallium Pyrrole 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Abdulla M, Svensson S, Haeger-Aronsen B (1979) Antagonistic effects of zinc and aluminum on lead inhibition of δ-aminolevulinic acid dehydratase. Arch Environ Health 34:464–469PubMedGoogle Scholar
  2. Alexopoulos CG, Chalevelakis G, Katsoulis C, Pallikaris G (1986) Adverse effects of cis-diamminedichloroplatinum II ( CDDP) on porphyrin metabolism in man. Cancer Chemother Pharmacol 17:165–170PubMedCrossRefGoogle Scholar
  3. Anderson PM, Desnick RJ (1980) Purification and properties of uroporphyrinogen I synthase from human erythrocytes. J Biol Chem 255:1993–1999PubMedGoogle Scholar
  4. Angle CR (1993) Childhood lead poisoning and its treatment. Annu Rev Pharmacol Toxicol 32:409–434CrossRefGoogle Scholar
  5. Astrin KH, Bishop DF, Wetmur JG, Kaul B, Davidow B, Desnick RJ (1987) δ-Aminolevulinic acid dehydratase isozymes and lead toxicity. Ann N Y Acad Sci 514:23–29PubMedCrossRefGoogle Scholar
  6. Baghurst PA, McMichael AJ, Wigg NR, Vimpani GV, Robertson EF, Roberts RJ, Tong S-L (1992) Environmental exposure to lead and children’s intelligence at the age of seven years. N Engl J Med 327:1279–1284PubMedCrossRefGoogle Scholar
  7. Batlle AM del C, Benson A, Rimington C (1965) Purification and properties of coproporphyrinogenase. Biochem J 97:731–740PubMedGoogle Scholar
  8. Benkmann HG, Bogdanski P, Goedda HW (1983) Polymorphism of delta-aminolevulinic acid dehydratase in various populations. Hum Hered 33:61–64CrossRefGoogle Scholar
  9. Bernard A, Lauwerys R (1987) Metal-induced alterations of δ-aminolevulinic acid dehydratase. Ann N Y Acad Sci 514:41–47PubMedCrossRefGoogle Scholar
  10. Bird TD, Hamernynik P, Nutter JY, Labbe RF (1979) Inherited deficiency of delta-aminolevulinic acid dehydratase. Am J Hum Genet 31:662–668PubMedGoogle Scholar
  11. Bonkovsky HL, Sinclair PR, Bement WJ, Lambrecht RW, Sinclair JF (1987) Role of cytochrome P-450 in porphyria caused by halogenated aromatic compounds. Ann N Y Acad Sci 514:96–112PubMedCrossRefGoogle Scholar
  12. Borup P, Vordac V, Pederson JS, With TK (1980) The porphyrin pattern of normal urine. Int J Biochem 12:1075–1079PubMedCrossRefGoogle Scholar
  13. Bowers MA, Aicher LD, Davis HA, Woods JS (1992) Quantitative determination of porphyrins in rat and human urine and evaluation of urinary porphyrin profiles during mercury and lead exposures. J Lab Clin Med 120:272–281PubMedGoogle Scholar
  14. Cantoni O, Evans RM, Costa M (1982) Similarity in the acute cytotoxic response of mammalian cells to mercury and X-rays:DNA damage and glutathion depletion. Biochem Biophys Res Commun 108:614–619PubMedCrossRefGoogle Scholar
  15. Cherian MG, Goyer RA, Delaquerriere-Richardson L (1976) Cadmium-metallothionein-induced nephropathy. Toxicol Appl Pharmacol 38:399–408PubMedCrossRefGoogle Scholar
  16. Chisolm JJ Jr (1971) Screening techniques for undue lead exposure in children:biological and practical considerations. J Pediatr 79:719–725PubMedCrossRefGoogle Scholar
  17. Clement RP, Kohashi K, Piper WN (1982) Rat hepatic uroporphyrinogen III cosynthase:purification, properties, and inhibition by metal ions. Arch Biochem Biophys 214:657–667PubMedCrossRefGoogle Scholar
  18. Dailey HA, Fleming JE (1983) Bovine ferrochelatase. Kinetic analysis of inhibition by N-methylprotoporphyrin, manganese and heme. J Biol Chem 258:11453–11459PubMedGoogle Scholar
  19. De Bruin A (1968) Effect of lead exposure on the level of δ-aminolevulinic dehydratase activity. Med Lav 59:411–418PubMedGoogle Scholar
  20. De Matteis F (1988) Role or iron in the hydrogen peroxide-dependent oxidation of hexahydroporphyrins (porphyrinogens):a possible mechanism for the exacerbation by iron of hepatic uroporphyria. Mol Pharmacol 33:463–469PubMedGoogle Scholar
  21. De Matteis F, Harvey C, Reed C, Hempenius R (1988) Increased oxidation of uroporphyrinogen by an inducible liver microsomal system. Biochem J 250:161–169PubMedGoogle Scholar
  22. De Salamanca RE, Molina C, Olmos A, Chinarro S, Perpina J, Munoz JJ, Pena ML, Vails V (1983) Excretion de porfirinas y precursores en ratas cronicamente intoxicadas por mercurio. Gastroenterol Hepatol 6:20–23Google Scholar
  23. Doss M, Muller WA (1982) Acute lead poisoning in inherited porphobilinogen synthase (aminolevulinic acid dehydrase) deficiency. Blut 45:131–139PubMedCrossRefGoogle Scholar
  24. Echeverria D, Heyer N, Woods JS, Martin MD, Naleway CA (1994) Effects of low-level exposure to elemental mercury among dentists. Neurotoxicol Teratol (to be published)Google Scholar
  25. Elder GH, Evans JO (1978) Evidence that coproporphyrinogen oxidase activity in rat liver is situated in the intermembrane space of mitochondrion. Biochem J 172:345–351PubMedGoogle Scholar
  26. Elder GH, Urquhart AJ (1984) Human uroporphyrinogen decarboxylase. Do tissue-specific isoenzymes exist? Biochem Soc Trans 12:663–664Google Scholar
  27. Elder GH, Tovey JA, Sheppard DM (1983) Purification of uroporphyrinogen decarboxylase from human erythrocytes. Biochem J 215:45–55PubMedGoogle Scholar
  28. Farant JP, Wigfield DC (1987) Interaction of divalent metal ions with normal and lead-inhibited human erythrocytic porphobilinogen synthetase in vitro. Toxicol Appl Pharmacol 89:9–18PubMedCrossRefGoogle Scholar
  29. Fell GS (1984) Lead toxicity:problems of definition and laboratory evaluation. Ann Clin Biochem 21:453–460PubMedGoogle Scholar
  30. Ferioli A, Harvey C, De Matteis F (1984) Drug-induced accumulation of uroporphyrin in chicken hepatocyte cultures. Biochem J 224:769–777PubMedGoogle Scholar
  31. Ford RE, Ou CN, Ellefson RD (1981) Liquid-chromatographic analysis for urinary porphyrins. Clin Chem 27:397–401PubMedGoogle Scholar
  32. Fowler BA, Mahaffey KR (1978) Interaction among lead, cadmium and arsenic in relation to porphyrin excretion patterns. Environ Health Perspect 25:87–90PubMedCrossRefGoogle Scholar
  33. Fowler BA, Woods JS (1977) Ultrastructural and biochemical changes in renal mitochondria following chronic oral methyl mercury exposure:the relationship to renal function. Exp Mol Pathol 27:403 - 412PubMedCrossRefGoogle Scholar
  34. Fowler BA, Kimmel CA, Woods JS, McConnell EE, Grant LD (1980) Chronic low level toxicity of lead in the rat. III. An integrated assessment of long-term toxicity with special reference to the kidney. Toxicol Appl Pharmacol 56:59–77PubMedCrossRefGoogle Scholar
  35. Francis JE, Smith AG (1988) Oxidation of uroporphyrinogen by free radicals. Evidence for nonporphyrin products as potential inhibitors of uroporphyrinogen decarboxylase. FEBS Lett 233:311–314PubMedCrossRefGoogle Scholar
  36. Garcia-Vargas GG, Garcia-Rangel A, Aguilar-Romo M, Garcia-Salcedo J, Maria del Razo L, Ostrosky-Wegman P, Cortinas de Nava C, Cebrian ME (1991) A pilot study on the urinary excretion of porphyrins in human populations chronically exposed to arsenic in Mexico. Hum Exp Toxicol 10:189–193PubMedCrossRefGoogle Scholar
  37. Gibson RD, Neuberger A, Scott JJ (1955) The purification and properties of δ-aminolevulinate dehydratase. Biochem J 61:618–629PubMedGoogle Scholar
  38. Goering PL, Fowler BA (1987) Mechanism of urinary excretion of δ-aminolevulinic acid after intrathecal instillation of gallium arsenide. Ann N Y Acad Sci 514:330–332CrossRefGoogle Scholar
  39. Goldwater LJ, Joselow MM (1967) Absorption and excretion of mercury in man. XII. Effects of mercury exposure on urinary excretion of coproporphyrin and delta-aminolevulinic acid. Arch Environ Health 15:327–331PubMedGoogle Scholar
  40. Goyer RA (1993) Lead toxicity:current concerns. Environ Health Perspect 100:177–187PubMedCrossRefGoogle Scholar
  41. Granick S, Sassa S (1971) δ-Aminolevulinic acid synthetase and the control of heme and chlorophyll synthesis. In:Vogel HJ (ed) Metabolic pathways, vol V, 3rd edn. Academic, New York, pp 77–141Google Scholar
  42. Haeger-Aronsen B (1960) Studies on urinary excretion of δ-aminolevulinic acid and other haem, precursors in lead workers and lead intoxicated rabbits. Scand J Clin Lab Invest 12 [Suppl 47]:1–28PubMedGoogle Scholar
  43. Haeger-Aronsen B (1982) Why is the patient with lead intoxication not light sensitive? Acta Dermatol 100 [Suppl]:67–71Google Scholar
  44. Henderson MJ, Toothill C (1983) Urinary coproporphyrin in lead intoxication:a study in the rabbit. Clin Sci 65:527–532PubMedGoogle Scholar
  45. Hermes-Lima M, Pereira B, Bechara EJH (1991) Are free radicals involved in lead poisoning? Xenobiotica 8:1095–1090Google Scholar
  46. Hernberg S, Nikkanen J (1970) Enzyme inhibition by lead under normal urban conditions. Lancet i:63–64CrossRefGoogle Scholar
  47. Hernberg S, Nikkanen J, Mellin G, Lilius H (1970) δ-Aminolevulinic acid dehydratase as a measure of lead exposure. Arch Environ Health 21:140–145PubMedGoogle Scholar
  48. Ho JW (1990) Determination of porphyrins in human blood by high performance liquid chromatography. J Liquid Chromatog 13:2179–2192CrossRefGoogle Scholar
  49. Ichiba M, Tomokuni K (1987) Urinary excretion of 5-hydroxyindoleacetic acid, δ- aminolevulinic acid and coproporphyrin isomers in rats and men exposed to lead. Toxicol Lett 38:91–96PubMedCrossRefGoogle Scholar
  50. Iscan M, Maines MD (1990) Differential regulation of heme and drug metabolism in rat testis and prostate:response to cis-platinum and human chorionic gonadotropin. J Pharmacol Exp Ther 253:73–79PubMedGoogle Scholar
  51. Jaffe EK, Bagla S, Michini PA (1991) Réévaluation of a sensitive indicator of early lead exposure. Biol Trace Element Res 28:223–231CrossRefGoogle Scholar
  52. Jones MS, Jones OTG (1969) The structural organization of heme synthesis in rat liver mitochondria. Biochem J 113:507–514PubMedGoogle Scholar
  53. Kardish R, Fowler BA, Woods JS (1980) Alteration in urinary coproporphyrin and hepatic coproporphyrinogen III oxidase activity following exposure to toxic metals. 19th annual meeting of the Society of Toxicology, abstract A125Google Scholar
  54. Labbe RF, Hubbard N (1961) Metal specificity of the iron-protoporphyrin chelating enzyme. Biochim Biophys Acta 52:131–135CrossRefGoogle Scholar
  55. Labbe RF, Finch CA, Smith NJ, Doan RN, Sood SK, Nishi M (1979) Erythrocyte protoporphyrin/heme ratio in the assessment of iron status. Clin Chem 25:87–92PubMedGoogle Scholar
  56. Labbe RF, Rettmer RL, Shah AG, Turnlund JR (1987) Zinc protoporphyrin. Past, present and future. Ann N Y Acad Sci 514:7–14PubMedCrossRefGoogle Scholar
  57. Lamola AA, Yamane T (1974) Zinc protoporphyrin in the erythrocytes of patients with lead intoxication and iron deficiency anaemia. Science 186:936–938PubMedCrossRefGoogle Scholar
  58. Lamola AA, Joselow M, Yamane T (1975) Zinc protoporphyrin (ZPP):a simple sensitive fluorometric screening test for lead poisoning. Clin Chem 21:93–97PubMedGoogle Scholar
  59. Lim CK, Peters TP (1984) Urine and faecal porphyrin profiles by reversed-phase high-performance liquid chromatography in the porphyrias. Clin Chem Acta 139:55–63CrossRefGoogle Scholar
  60. Lund B, Miller DM, Woods JS (1991) Mercury-induced H2O2 production and lipid peroxidation in vitro in rat kidney mitochondria. Biochem Pharmacol 42:S181–S187PubMedCrossRefGoogle Scholar
  61. Lund BO, Miller DM, Woods JS (1993) Studies on Hg(II)-induced H2O2 formation and oxidative stress in vivo and in vitro in rat kidney mitochondria. Biochem Pharmacol 45:2017–2024PubMedCrossRefGoogle Scholar
  62. Maines MD (1984) New developments in the regulation of heme metabolism and their implications. Crit Rev Toxicol 12:241–314PubMedCrossRefGoogle Scholar
  63. Maines MD (1986) Differential effect of cis-platinum (cis-diammine-dichloro-platinum) on the regulation of liver and kidney heme and hemoprotein metabolism:possible involvement of γ-glutamyl cycle enzymes. Biochem J 237:713–721PubMedGoogle Scholar
  64. Maines MD (1990) Effect of cis-platinum on heme, drug, and steroid metabolism pathways:possible involvement in nephrotoxicity and infertility. Crit Rev Toxicol 21:1–20PubMedCrossRefGoogle Scholar
  65. Maines MD, Kappas A (1977) Enzymes of heme metabolism in the kidney. J Exp Med 146:1286–1293PubMedCrossRefGoogle Scholar
  66. Marks GS (1985) Exposure to toxic agents:the heme biosynthetic pathway and hemoproteins as indicator. Crit Rev Toxicol 15:151–179PubMedCrossRefGoogle Scholar
  67. Martinez G, Cebrian M, Chamorro G, Jauge P (1983) Urinary uroporphyrin as an indicator of arsenic exposure in rats. Proc West Pharmacol Soc 26:171PubMedGoogle Scholar
  68. Mayo Medical Laboratories Interpretive Handbood (1990) Mayo Medical Laboratories, Rochester, MN, pp 149–152Google Scholar
  69. Meredith PA, Moore MR, Goldberg A (1974) The effects of aluminum, lead and zinc on δ-aminolevulinic acid dehydratase. Biochem Soc Trans 2:1243–1245Google Scholar
  70. Millar JA, Cumming RL, Battistini V, Cabswell F, Goldberg A (1970) Lead and δ- aminolevulinic acid dehydratase levels in mentally retarded children and in lead-poisoned suckling rats. Lancet ii:695–698CrossRefGoogle Scholar
  71. Miller DM, Woods JS (1993) Redox activities of mercury-thiol complexes:Implications for mercury-induced porphyria and toxicity. Chem Biol Interact 88:23–35PubMedCrossRefGoogle Scholar
  72. Miller DM, Lund B, Woods JS (1991) Reactivity of Hg(II) with superoxide:evidence for the catalytic dismutation of superoxide by Hg(II). J Biochem Toxicol 6:293–298PubMedCrossRefGoogle Scholar
  73. Mukerji S, Pimstone N (1990) Free radical mechanism of oxidation of uroporphyrinogen in the presence of ferrous iron. Arch Biochem Biophys 281:177–184PubMedCrossRefGoogle Scholar
  74. Nakemura M, Yasuhochi Y, Minokami S (1975) Effects of cobalt on heme biosynthesis in rat liver and spleen. J Biochem 78:373–380Google Scholar
  75. Naleway C, Chou H-N, Muller T, Dabney J, Roxe D, Siddiqui F (1991) On-site screening for urinary Hg concentrations and correlation with glomerular and renal tubular function. J Public Health Dent 51:12–17PubMedCrossRefGoogle Scholar
  76. Needleman HL, Gatsonis CA (1990) Low-level lead exposure and the IQ of children. J Am Med Assoc 263:673–678CrossRefGoogle Scholar
  77. Nordman Ch, Hernberg S, Nikkanen J, Rykanen A (1973) Blood lead levels and erythrocyte δ-aminolevulinic acid dehydratase activity in people living around a secondary lead smelter. Work Environ Health 10:19–25Google Scholar
  78. Ockner RK, Schmid R (1961) Acquired porphyria in man and rat due to hexachlorobenzene intoxication. Nature 189:499PubMedCrossRefGoogle Scholar
  79. Omae K, Sakurai H, Higashi T, Hosoda K, Teruya K, Suzuki Y (1988) Reevaluation of urinary excretion of coproporphyrins in lead-exposed workers. Int Arch Occup Environ Health 60:107–110PubMedCrossRefGoogle Scholar
  80. Piomelli S, Davidow B (1972) Free erythrocyte protoporphyrin concentration:a promising screening test for led poisoning. Pediatr Res 6:366Google Scholar
  81. Piomelli S, Young P, Gay G (1972) A micromethod forree erythrocyte porphyrins:the FEP test. J Lab Clin Med 81:932–940Google Scholar
  82. Piomelli S, Davidow B, Guinee VF, Young P, Gay G (1973) The FEP (free erythrocyte porphyrins) test:a screening micromethod for lead poisoning. Pediatrics 51:254–259PubMedGoogle Scholar
  83. Piomelli S, Lamola AA, Poh-Fitzpatrick MB, Seaman C, Harber L (1975) Erythropoietic protoporphyria and Pb intoxication:the molecular basis for difference in cutaneous sensitivity. I. Different rates of diffusion of protoporphyrin from erythrocytes, both in vivo and in vitro. J Clin Invest 56:1519–1527PubMedCrossRefGoogle Scholar
  84. Piomelli S, Seaman C, Kapoor S (1987) Lead-induced abnormalities of porphyrin metabolism. The relationship with iron deficiency. Ann N Y Acad Sci 514:278–288PubMedCrossRefGoogle Scholar
  85. Piper WN, Tephly TR (1974) Differential inhibition of erythrocyte and hepatic uroporphyrinogen I synthetase activity by lead. Life Sci 14:873–876PubMedCrossRefGoogle Scholar
  86. Piper WN, van Lier RBL (1977) Pteridine regulation of inhibition of hepatic uroporphyrinogen I synthetase activity by lead chloride. Mol Pharmacol 13:1126–1135PubMedGoogle Scholar
  87. Piper WN, Tse J, Clement RP, Kohashi M (1983) Evidence for a folate bound to rat hepatic uroporphyrinogen III cosynthase and its role in the biosynthesis of heme. In:Blair IA (ed) Chemistry and biology of pteridines. De Gruyter, Berlin, p 415Google Scholar
  88. Poulson R (1976) The enzymatic conversion of protoporphyrinogen IX to protoporphyrin IX in mammalian mitochondria. J Biol Chem 251:3730–3733PubMedGoogle Scholar
  89. Quinlan GJ, Halliwell B, Moorhouse CP, Gutteridge JMC (1988) Action of lead and aluminum ions on iron-stimulated lipid peroxidation in liposomes, erythrocytes and rat liver microsomal fractions. Biochim Biophys Acta 962:196–200PubMedGoogle Scholar
  90. Roels H, Buchet JP, Lauwerys R, Hubermont G, Bruaux P, Claeys-Thoreau F, Lafontaine A, Van Overschelde J (1976) Impact of air pollution by lead on the heme biosynthesis pathway in school-age children. Arch Environ Health 31:310–316PubMedGoogle Scholar
  91. Rossi E, Attwood PV, Garcia-Webb P (1992) Inhibition of human coproporphyrinogen oxidase activity by metals, bilirubin and haemin. Biochim Biophys Acta 1135:262–268PubMedCrossRefGoogle Scholar
  92. Rossi E, Taketani S, Garcia-Webb P (1993) Lead and the terminal mitochondrial enzymes of haem synthesis. Biomed Chromatog 7:1–6CrossRefGoogle Scholar
  93. San Martin de Viale LC, Viale AA, Nacht S, Grinstein M (1970) Experimental porphyria induced in rats by hexachlorobenzene. A study of the porphyrins excreted by urine. Clin Chem Acta 28:13–17CrossRefGoogle Scholar
  94. Sassa S (1978) Toxic effects of lead, with particular reference to porphyrin and heme metabolism. In:DeMatteis F, Aldridge WN (eds) Heme and hemoproteins, chap 11. Springer, Berlin Heidelberg New York, pp 333–371Google Scholar
  95. Sears WG, Eales L (1973) Aluminum-induced porphyria in the rat. IRCS International Research Communication System J (73–11) 3–10–35Google Scholar
  96. Sheehra JS, Gore MG, Chaudhry AG, Jordan PM (1981) δ-Aminolevulinic acid dehydratase: the role of sulphydryl groups in 5-ALA dehydratase from bovine liver. Eur J Biochem 114:263–269CrossRefGoogle Scholar
  97. Simmonds PL, Luckhurst CL, Woods JS (1994) Quantitative evaluation of heme biosynthetic pathway parameters as biomarkers of low level lead exposure in rats. J Toxicol Environ Health (in press)Google Scholar
  98. Sinclair PR, Lambrecht R, Sinclair J (1987) Evidence for cytochrome P-450-mediated oxidation of uroporphyrinogen by cell-free liver extracts from chick embryos treated with 3-methylcholanthrene. Biochem Biophys Res Commun 146:1324–1329PubMedCrossRefGoogle Scholar
  99. Smith AG, Francis JE (1987) Chemically-induced formation of an inhibitor of hepatic uroporphyrinogen decarboxylase in inbred mice with iron overload. Biochem J 246:221–226PubMedGoogle Scholar
  100. Sun J, Wang J, Liu J (1992) Effects of lead exposure on porphyrin metabolism indicators in smelter workers. Biomed Environ Sci 5:76–85PubMedGoogle Scholar
  101. Sunderman FW Jr (1986) Metals and lipid peroxidation. Acta Pharmacol Toxicol 59 [Suppl 7]:248–255Google Scholar
  102. Taketani S, Tokunaga R (1981) Rat liver ferrochelatase:purification, properties and stimulation by fatty acids. J Biol Chem 256:12748–12753PubMedGoogle Scholar
  103. Taketani S, Tanaka A, Tokunaga R (1985) Reconstitution of heme-synthesizing activity from ferric ion and porphyrins, and the effect of lead on the activity. Arch Biochem Biophys 242:291–296PubMedCrossRefGoogle Scholar
  104. Taketani S, Tanaka-Yoshioka A, Masaki R, Tashiro Y, Tokunaga R (1986) Association of ferrochelatase with complex I in bovine heart mitochondria. Biochim Biophys Acta 883:227–283Google Scholar
  105. Taljaard JJF, Shanley BC, Deppe WM, Joubert SM (1972) Porphyrin metabolism in experimental hepatic siderosis in the rat. II. Combined effect of iron overload and hexachlorobenzene. Br J Haematol 23:513–517PubMedCrossRefGoogle Scholar
  106. Telolahy P, Javelaud B, Cluet J, de Ceaurriz J, Boudene C (1993) Urinary excretion of porphyrins by smelter workers chronically exposed to arsenic dust. Toxicol Lett 66:89–95PubMedCrossRefGoogle Scholar
  107. Tephly TR, Hasegawa D, Baron J (1971) Effects of drugs on heme synthesis in the liver. Metabolism 20:200–210PubMedCrossRefGoogle Scholar
  108. Tsukamoto Y, Iwanami S, Marumo F (1980) Disturbances of trace element concentrations in plasma of patients with chronic renal failure. Nephron 26:174–179PubMedCrossRefGoogle Scholar
  109. Watson CJ (1946) Some newer concepts of the natural derivatives of hemoglobin. Blood 1:99–120PubMedGoogle Scholar
  110. Webb DR, Sipes IG, Carter DE (1984) In vitro solubility and in vivo toxicity of gallium arsenide. Toxicol Appl Pharmacol 76:96–104PubMedCrossRefGoogle Scholar
  111. Weisberg JB, Lipschultz F, Osko FA (1971) δ-Aminolevulinic acid dehydratase activity in circulating blood cells: a sensitive laboratory test for the detection of childhood lead poisoning. N Engl J Med 284:565–569CrossRefGoogle Scholar
  112. Westerlund J, Pudek M, Schreiber WE (1988) A rapid and accurate spectrophotometric method for quantification and screening of urinary porphyrins. Clin Chem 34:345–351PubMedGoogle Scholar
  113. Wetmur JG, Lehnert G, Desnick RJ (1991) The δ-aminolevulinate dehydrase polymorphism:higher blood lead levels in lead workers and environmentally exposed children with the 1–2 and 2–2 isozymes. Environ Res 56:109–119PubMedCrossRefGoogle Scholar
  114. Woods JS (1988a) Attenuation of porphyrinogen oxidation by glutathione and reversal by porphyrinogenic trace metals. Biochem Biophys Res Commun 152:1428–1434PubMedCrossRefGoogle Scholar
  115. Woods JS (1988b) Regulation of porphyrin and heme metabolism in the kidney. Semin Hematol 25:336–348PubMedGoogle Scholar
  116. Woods JS (1989) Mechanisms of metal-induced alterations of cellular heme metabolism. Comments Toxicol 3:3–25Google Scholar
  117. Woods JS, Calas CA (1989) Iron stimulation of free radical-mediated porphyrinogen oxidation by hepatic and renal mitochondria. Biochem Biophys Res Comm 160:101–108PubMedCrossRefGoogle Scholar
  118. Woods JS, Fowler BA (1977) Renal porphyrinuria during chronic methyl mercury exposure. J Lab Clin Med 90:266–272PubMedGoogle Scholar
  119. Woods JS, Fowler BA (1978) Altered regulation of mammalian hepatic heme biosynthesis and uroporphyrin excretion during prolonged exposure to sodium arsenate. Toxicol Appl Pharmacol 43:361–371PubMedCrossRefGoogle Scholar
  120. Woods JS, Fowler BA (1982) Selective inhibition of delta-aminolevulinic acid dehydratase by indium chloride in rat kidney:biochemical and ultrastructural studies. Exp Mol Pathol 36:306–315PubMedCrossRefGoogle Scholar
  121. Woods JS, Fowler BA (1987) Metal alteration of uroporphyrinogen decarboxylase and coproporphyrinogen oxidase. Ann N Y Acad Sci 514:55–64PubMedCrossRefGoogle Scholar
  122. Woods JS, Southern MR (1989) Studies on the etiology of trace metal-induced porphyria:effects of porphyrinogenic metals on coproporphyrinogen oxidase in rat liver and kidney. Toxicol Appl Pharmacol 97:183–190PubMedCrossRefGoogle Scholar
  123. Woods JS, Miller HD (1993) Quantitative measurement of porphyrins in biological tissues and evaluation of tissue porphyrins during toxicant exposures. Fundam Appl Toxicol 21:291–297PubMedCrossRefGoogle Scholar
  124. Woods JS, Kardish RM, Fowler BA (1981) Studies on the action of porphyrinogenic trace metals on the activity of hepatic uroporphyrinogen decarboxylase. Biochem Biophys Res Commun 103:264–271PubMedCrossRefGoogle Scholar
  125. Woods JS, Eaton DL, Lukens CB (1984) Studies on porphyrin metabolism in the kidney. Effects of trace metals and glutathione on renal uroporphyrinogen decarboxylase. Mol Pharmacol 26:366–341Google Scholar
  126. Woods JS, Calas CA, Aicher LD, Robinson BH, Mailer C (1990a) Stimulation of porphyrinogen oxidation by mercuric ion. I. Evidence of free radical formation in the presence of thiols and hydrogen peroxide. Mol Pharmacol 38:253–260Google Scholar
  127. Woods JS, Calas CA, Aicher LD (1990b) Stimulation of porphyrinogen oxidation by mercuric ion. II. Promotion of oxidation from the interaction of mercuric ion, glutathione, and mitochondria-generated hydrogen peroxide. Mol Pharmacol 38:261–266Google Scholar
  128. Woods JS, Bowers MA, Davis HA (1991) Urinary porphyrin profiles as biomarkers of trace metal exposure and toxicity:studies on urinary porphyrin excretion patterns in rats during prolonged exposure to methyl mercury. Toxicol Appl Pharmacol 110:464–476PubMedCrossRefGoogle Scholar
  129. Woods JS, Martin MD, Naleway CA, Echeverría D (1993) Urinary porphyrin profiles as a biomarker of mercury exposure:studies in dentists with occupational exposure to mercury vapor. J Toxicol Environ Health 40:239–250Google Scholar
  130. Yamanaka K, Hoshino M, Okamoto M, Sawamura R, Hasegawa A, Okada S (1990) Induction of DNA damage by dimethylarsine, a metabolite of inorganic arsenics, is for the major part likely due to its peroxyl radical. Biochem Biophys Res Commun 168:58–64PubMedCrossRefGoogle Scholar
  131. Yoshinaga T, Sano S (1980) Coproporphyrinogen oxidase. II. Reaction mechanism and role of tyrosine residues on the activity. J Biol Chem 255:4727–4731PubMedGoogle Scholar
  132. Zwennis WCM, Franssen AC, Wijnans MJ (1990) Use of zinc protoporphyrin in screening individuals for exposure to lead. Clin Chem 36:1456–1459PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1995

Authors and Affiliations

  • J. S. Woods

There are no affiliations available

Personalised recommendations