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Toxicology of Inhaled Materials pp 421–470Cite as

The Pulmonary Mixed-Function Oxidase System

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Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 75))

Abstract

In 1974 Tierney wrote: “In terms of phylogeny, the lung is a relatively new organ, but it has been in existence longer than have biochemists and physiologists. Why, then, have its metabolism and biochemistry been ignored until recently?” Since then, considerable progress has been made in our knowledge of basic lung biochemistry, including the pulmonary mixed-function oxidase or monooxygenase system. Much of this recent research has been spurred by the need to identify and quantify the pulmonary effects of a variety of inhaled toxic pollutants and synthetic pneumotoxins.

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References

  • Abramson RK, Hutton J J (1975) Effects of cigarette smoking on aryl hydrocarbon hydroxylase activity in lungs and tissues of inbred mice. Cancer Res 35:23–29

    PubMed  CAS  Google Scholar 

  • Adamson IYR, Bowden DH (1974) The pathogenesis of bleomycin-induced pulmonary fibrosis in mice. Am J Pathol 77:185–189

    PubMed  CAS  Google Scholar 

  • Allen JR, Chesney CF, Frazee WJ (1972) Modifications of pyrrolizidine alkaloid intoxication resulting from altered hepatic microsomal enzymes. Toxicol Appl Pharmacol 23:470–479

    PubMed  CAS  Google Scholar 

  • Arinc E, Philpot RM (1976) Preparation and properties of partially purified pulmonary cytochrome P-450 from rabbits. J Biol Chem 251:3213–3220

    PubMed  CAS  Google Scholar 

  • Autor AP (1974) Reduction of paraquat toxicity by superoxide dismutase. Life Sci 14:1309–1319

    PubMed  CAS  Google Scholar 

  • Bakhle YS, Vane JR (1974) Pharmacokinetic function of the pulmonary circulation. Physiol Rev 54:1007–1045

    PubMed  CAS  Google Scholar 

  • Bend JR, Hook GE, Easterling RE, Gram TE, Fouts JR (1972) A comparative study of the hepatic and pulmonary mixed-function oxidase systems in the rabbit. J Pharmacol Exp Ther 183:206–217

    PubMed  CAS  Google Scholar 

  • Bend JR, Hook GE, Gram TE (1973) Characterization of lung microsomes as related to drug metabolism. Drug Metab Dispos 1:358–367

    PubMed  CAS  Google Scholar 

  • Bilimoria MH, Johnson J, Hogg JC, Witsehi HP (1977) Pulmonary aryl hydrocarbon hydroxylase: tobacco smoke-exposed guinea pigs. Toxicol Appl Pharmacol 41:433–440

    PubMed  CAS  Google Scholar 

  • Block ER (1979) Potentiation of acute paraquat toxicity by vitamin E deficiency. Lung 156:195–203

    PubMed  CAS  Google Scholar 

  • Blum RH, Carter SK, Agre K (1983) A clinical review of bleomycin — a new antineoplastic agent. Cancer 31:903–912

    Google Scholar 

  • Boyd MR (1976) Role of metabolic activation in the pathogenesis of chemically-induced pulmonary disease: mechanism of action of the lung-toxic furan, 4-ipomeanol. Environ Health Perspect 16:127–128

    PubMed  CAS  Google Scholar 

  • Boyd MR (1977) Evidence for the Clara cell as a site of cytochrome P-450-dependent mixed-function oxidase activity in lung. Nature 269:713–715

    PubMed  CAS  Google Scholar 

  • Boyd MR (1980a) Biochemical mechanisms of chemical-induced lung injury: role of metabolic activation. CRC Crit Rev Toxicol 7:103–176

    CAS  Google Scholar 

  • Boyd MR (1980b) Biochemical mechanisms in pulmonary toxicity of furan derivatives. Rev Biochem Toxicol 2:71–101

    CAS  Google Scholar 

  • Boyd MR (1980c) Effects of inducers and inhibitors on drug-metabolizing enzymes and on drug toxicity in extrahepatic tissues. Ciba Found 76:43–66

    CAS  Google Scholar 

  • Boyd MR, Burka LT (1978) In vivo studies on the relationship between target organ alkyl-ation and the pulmonary toxicity of a chemically reactive metabolite of 4-ipomeanol. J Pharmacol Exp Ther 207:687–697

    PubMed  CAS  Google Scholar 

  • Boyd MR, Neal RA (1976) Studies on the mechanisms of toxicity and the development of tolerance to the pulmonary toxin, α-naphthylthiourea (ANTU). Drug Metab Dispos 4:314–322

    PubMed  CAS  Google Scholar 

  • Boyd MR, Burka LT, Wilson BJ (1975) Distribution, excretion, and binding of radioactivity in the rat after intraperitoneal administration of the lung-toxic furan 14C-4-ipomeanol. Toxicol Appl Pharmacol 32:147–157

    PubMed  CAS  Google Scholar 

  • Boyd MR, Burka LT, Wilson BJ, Sasame HA (1978a) In vivo studies on the metabolic activation of the pulmonary toxin, 4-ipomeanol, by rat lung and liver microsomes. J Pharmacol Exp Ther 207:677–686

    PubMed  CAS  Google Scholar 

  • Boyd MR, Statham CN, Franklin RB, Mitchell JR (1978b) Pulmonary bronchiolar alkyl-ation and necrosis by 3-methylfuran, a naturally occurring potential atmospheric contaminant. Nature 272:270–271

    PubMed  CAS  Google Scholar 

  • Boyd MR, Catignani GL, Sasame HA, Mitchell JR, Stiko AW (1979a) Acute pulmonary injury in rats by nitrofurantoin and modification by vitamin E, dietary fat, and oxygen. Am Rev Resp Dis 120:93–99

    PubMed  CAS  Google Scholar 

  • Boyd MR, Dutcher JS, Buckpitt AR, Jones RB, Statham CN (1979b) Role of metabolic activation in extrahepatic target organ alkylation in the cytotoxicity by 4-ipomeanol, a furan derivative from moldy sweet potatoes: possible implications for carcinogenesis. In: Miller EC, Miller JA, Hirono I, Sugamura T, Takayama S (eds) Naturally occurring carcinogens-mutagens and modulators of carcinogenesis. University Park Press, Baltimore, pp 35–56

    Google Scholar 

  • Boyd MR, Stiko AW, Sasame HA (1979c) Metabolic activation of nitrofurantoin-possible implications for carcinogenesis. Biochem Pharmacol 28:601–606

    PubMed  CAS  Google Scholar 

  • Boyd MR, Sasame HA, Franklin RB (1980a) Comparison of ratios of covalent binding to total metabolism of the pulmonary toxin, 4-ipomeanol, in vitro in pulmonary and hepatic microsomes, and the effects of pretreatments with phenobarbital or 3-methyl-cholanthrene. Biochem Biophys Res Comm 93:1167–1172

    PubMed  CAS  Google Scholar 

  • Boyd MR, Statham CN, Longo NS (1980b) The pulmonary Clara cell as a target for toxic chemicals requiring metabolic activation: studies with carbon tetrachloride? J Pharmacol Expt Ther 212:109–114

    CAS  Google Scholar 

  • Boyland E (1980) The history and future of chemical carcinogenesis. Br Med Bull 36:5–10

    PubMed  CAS  Google Scholar 

  • Bradley BJ, Carlson JR (1980) Ultrastructural pulmonary changes induced by intravenously administered 3-methylindole in goats. Am J Pathol 99:551–560

    PubMed  CAS  Google Scholar 

  • Bray TM, Carlson JR (1980) Tissue and subcellular distribution and excretion of 3-[14C]methylindole in rabbits after intratracheal infusion. Can J Physiol Pharmacol 58:1399–1405

    PubMed  CAS  Google Scholar 

  • Bresnick E (1979) Nuclear activation of polycyclic hydrocarbons. Drug Metab Rev 10:209–223

    PubMed  CAS  Google Scholar 

  • Breyer U (1971) Metabolism of the phenothiazine drug perazine by liver and lung microsomes from various species. Biochem Pharmacol 20:3341–3351

    PubMed  CAS  Google Scholar 

  • Brodie BB, Reid WD, Cho AK, Sipes G, Krishna G, Gillette JR (1971) Possible mechanism of liver necrosis caused by aromatic organic compounds. Proc Natl Acad Sci USA 68:160–164

    PubMed  CAS  Google Scholar 

  • Brown EAB (1974) The localization, metabolism, and effects of drugs and toxicants in lung. Drug Metab Rev 3:33–87

    PubMed  CAS  Google Scholar 

  • Buckpitt A, Boyd M (1978) Xenobiotic metabolism in birds, species lacking pulmonary Clara cells. The Pharmacologist 20:181

    Google Scholar 

  • Buckpitt AR, Boyd MR (1982) Metabolic Activation of 4-Ipomeanol by Avian Tissue Microsomes. Toxicol Appl Pharmacol 65:53–62

    PubMed  CAS  Google Scholar 

  • Buege J A, Aust SD (1975) Comparative studies of rat liver and lung NADPH cytochrome c reductase. Bioehim Biophys Acta 385:371–379

    CAS  Google Scholar 

  • Buening MK, Wislocki PG, Levin W, Yagi H, Thakker DR, Akagi H, Koreeda M, Jerina DM, Conney AH (1978) Tumorigenicity of the optical enantiomers of the diastereomeric benzo[a]pyrene 7,8-diol-9,10-epoxides in newborn mice: exceptional activity of (+)-7β,8α-dihydroxy-9α, 10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene. Proc Natl Acad Sci USA 75:5358–5361

    PubMed  CAS  Google Scholar 

  • Burger RM, Peisach J, Horwitz SB (1981) Mechanism of bleomycin action: in vitro studies: Life Sci 28:715–727

    PubMed  CAS  Google Scholar 

  • Burke MD, Prough RA (1976) Some characteristics of hamster liver and lung microsomal aryl hydrocarbon (biphenyl and benzo(a)pyrene) hydroxylation reactions. Biochem Pharmacol 25:2187–2195

    PubMed  CAS  Google Scholar 

  • Burke MD, Prough RA, Mayer RT (1977) Characteristics of a microsomal cytochrome P-448-mediated reaction: ethoxyresorufin O-deethylation. Drug Metab Dispos 5:1–8

    PubMed  CAS  Google Scholar 

  • Bürki K, Stroming TH, Bresnick E (1974) Effects of an epoxide hydrase inhibitor on in vitro binding of polycyclic hydrocarbons to DNA and on skin carcinogenesis. J Natl Cancer Inst 52:785–788

    PubMed  Google Scholar 

  • Bus JS, Aust SD, Gibson JE (1974) Superoxide and single oxygen-catalyzed lipid peroxidation as a possible mechanism for paraquat (methyl viologen) toxicity. Biochem Biophys Res Commun 58:749–755

    PubMed  CAS  Google Scholar 

  • Bus JS, Aust SD, Gibson JE (1976) Paraquat toxicity: proposed mechanism of action involving lipid peroxidation. Environ Health Perspect 16:139–146

    PubMed  CAS  Google Scholar 

  • Butler C, Kleinerman J (1971) Paraquat in the rabbit. Br J Ind Med 28:67–71

    PubMed  CAS  Google Scholar 

  • Butler WH, Mattocks AR, Barnes JM (1970) Lesions in the liver and lungs of rats given pyrrole derivatives of pyrrolizidine alkaloids. J Pathol 100:169–175

    PubMed  CAS  Google Scholar 

  • Cantrell ET, Busbee D, Warr G, Martin R (1973a) Induction of aryl hydrocarbon hydroxylase in human leucocytes and pulmonary alveolar macrophages: a comparison. Life Sci 13:1649–1654

    PubMed  CAS  Google Scholar 

  • Cantrell ET, Warr GA, Busbee DL, Martin RR (1973b) Induction of aryl hydrocarbon hydroxylase in human pulmonary alveolar macrophages by cigarette smoking. J Clin Invest 52:1881–1884

    PubMed  CAS  Google Scholar 

  • Capdevila J, Jakobsson SW, Jernstrom B, Helia O, Orrenius S (1975) Characterization of a rat lung microsomal fraction obtained by Sepharose 2B ultrafiltration. Cancer Res 35:2820–2829

    PubMed  CAS  Google Scholar 

  • Carlone MF, Fouts JR (1974) In vitro metabolism of p-xylene by rabbit lung and liver. Xenobiotica 4:705–715

    CAS  Google Scholar 

  • Carlson JR, Yokoyama MT, Dickinson EO (1972) Induction of pulmonary edema and emphysema in cattle and goats with 3-methylindole. Science 176:298–299

    PubMed  CAS  Google Scholar 

  • Chen W-J, Chi EY, Smuckler EA (1977) Carbon-tetraehloride-induced changes in mixed function oxidases and microsomal cytochromes in the rat lung. Lab Invest 36:388–394

    PubMed  CAS  Google Scholar 

  • Clark DG, McElligot TF, Hurst EW (1966) The toxicity of paraquat. Br J Ind Med 23:126–132

    PubMed  CAS  Google Scholar 

  • Collis CH (1980) Lung damage from cytotoxic drugs. Cancer Chemother Pharmacol 4:17–27

    PubMed  CAS  Google Scholar 

  • Conney AH (1967) Pharmacological implications of microsomal enzyme induction. Pharmacol Rev 19:317–366

    PubMed  CAS  Google Scholar 

  • Conney AH, Miller EC, Miller J A (1957) Substrate-induced synthesis and other properties of benzpyrene hydroxylase in rat liver. J Biol Chem 228:753–766

    PubMed  CAS  Google Scholar 

  • Conning DM, Fletcher K, Swann AAB (1969) Paraquat and related bypyridyls. Br Med Bull 25:245–249

    PubMed  CAS  Google Scholar 

  • Crapo JD, Tierney DF (1974) Superoxide dismutase and pulmonary oxygen toxicity. Am J Physiol 226:1401–1405

    PubMed  CAS  Google Scholar 

  • Cunningham AL, Hurley JV (1972) Alphanaphthylthiourea-induced pulmonary edema in the rat: a topographical and electronmieroscope study. J Pathol 106:25–34

    PubMed  CAS  Google Scholar 

  • Daudel P, Duquesne M, Vigny P, Grover PL, Sims P (1975) Fluorescence spectral evidence that benzo[a]pyrene-DNA products in mouse skin arise from diol-epoxides. FEBS Lett 57:250–253

    PubMed  CAS  Google Scholar 

  • Dees JH, Coe LD, Yasukochi Y, Masters BS (1980) Immunofluorescence of NADPH-cytochrome c (P-450) reductase in rat and minipig tissues injected with phenobarbital. Science 208:1473–1475

    PubMed  CAS  Google Scholar 

  • Devereux TR, Fouts JR (1974) N-oxidation and demethylation of N,N-dimethylaniline by rabbit liver and lung microsomes: effects of age and metals. Chem Biol Interact 8:91–105

    PubMed  CAS  Google Scholar 

  • Devereux TR, Fouts JR (1980a) A procedure for isolation of rabbit pulmonary epithelial cells for study of foreign compound metabolism. In: Coon MJ, Conney AH, Estabrook RW, Gelboin HV, Gillette JR, O’Brien PJ (eds) Microsomes, drug oxidations, and chemical carcinogenesis. Academic, New York, pp 825–828

    Google Scholar 

  • Devereux TR, Fouts JR (1980b) Isolation and identification of Clara cells from rabbit lung. In Vitro 16:958–968

    PubMed  CAS  Google Scholar 

  • Devereux TR, Hook GE, Fouts JR (1979) Foreign compound metabolism by isolated cells from rabbit lung. Drug Metab Dispos 7:70–75

    PubMed  CAS  Google Scholar 

  • Devereux T, Smith B, Bend J, Fouts J (1981a) Xenobiotic metabolism in Clara and type II cells isolated from rabbit lung. The Pharmacologist 23:172

    Google Scholar 

  • Devereux TR, Serabjit-Singh CJ, Slaugher SR, Wolf CR, Philpot RM, Fouts JR (1981b) Identification of cytochrome P-450 isozymes in nonciliated bronchiolar epithelial (Clara) and alveolar type II cells isolated from rabbit lung. Exp Lung Res 2:221–230

    PubMed  CAS  Google Scholar 

  • Dieke SH, Richter CP (1945) Acute toxicity of thiourea to rats in relation to age, diet, strain, and species variation. J Pharmacol Exp Ther 83:195–201

    CAS  Google Scholar 

  • Dutcher JS, Boyd MR (1979) 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 28:3367–3372

    PubMed  CAS  Google Scholar 

  • Ferguson HC (1966) Effect of red cedar chip bedding on hexobarbital and pentobarbital sleep time. J Pharm Sci 55:1142–1143

    Google Scholar 

  • Fisher AB, Huber GH, Furia L (1977) Cytochrome P-450 content and mixed function oxidation by microsomes from rabbit alveolar macrophages. J Lab Clin Med 90:101–108

    PubMed  CAS  Google Scholar 

  • Fisher HK, Clements JA, Wright RB (1973) Enhancement of oxygen toxicity by the herbk cide paraquat. Am Rev Resp Dis 107:246–252

    PubMed  CAS  Google Scholar 

  • Fouts JR, Devereux TR (1972) 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 Expt Ther 183:458–468

    CAS  Google Scholar 

  • Fouts JR, Devereux TR (1973) Use of 10 sec sonication of homogenates to increase microsomal yield in liver and lung from young adult Dutch belt rabbits. Biochem Pharmacol 22:1393–1396

    PubMed  CAS  Google Scholar 

  • Fridovich I (1978) The biology of oxygen radicals. Sciene 201:875–880

    CAS  Google Scholar 

  • Gage JC (1968) The action of paraquat and diquat on the respiration of liver cell fractions. Biochem J 109:757–761

    PubMed  CAS  Google Scholar 

  • Gelboin HV, Blackburn NR (1964) The stimulatory effect of 3-methylcholanthrene on benzpyrene hydroxylase activity in several rat tissues: inhibition by actinomycin D and puromycin. Cancer Res 24:356–360

    PubMed  CAS  Google Scholar 

  • Gelboin HV, Selkirk JK, Yang SK, Wiebel FJ, Namoto, N (1976) Benzo[a]pyrene metabolism by mixed-function oxygenases, hydratases, and glutathione S-transferases: analysis by high pressure liquid chromatography. In: Arias IM, Jakoby WB (eds) Glutathione: metabolism and function. Raven, New York, pp 339–356

    Google Scholar 

  • Gielen JR, Goujon FM, Nebert DW (1972) Genetic regulation of aryl hydrocarbon hydroxylase induction. II. Simple Mendelian expression in mouse tissues in vivo. J Biol Chem 247:1125–1137

    PubMed  CAS  Google Scholar 

  • Gillette JR (1974a) A perspective on the role of chemically reactive metabolites of foreign compounds in toxicity. I. Correlation of changes in covalent binding of reactive metabolites with changes in the incidence and severity of toxicity. Biochem Pharmacol 23:2785–2794

    PubMed  CAS  Google Scholar 

  • Gillette JR (1974b) A perspective on the role of chemically reactive metabolites of foreign compounds in toxicity. II. Alterations in the kinetics of covalent binding. Biochem Pharmacol 23:2927–2938

    PubMed  CAS  Google Scholar 

  • Gillette JR, Mitchell JR, Brodie BB (1974) Biochemical mechanisms of drug toxicity. Annu Rev Pharmacol 14:271–288

    CAS  Google Scholar 

  • Gilman AG, Conney AH (1963) The induction of aminoazo dye N-demethylase in nonhepatic tissues by 3-methylcholanthrene. Biochem Pharmacol 12:591–593

    PubMed  CAS  Google Scholar 

  • Gould KG, Clements JA, Jones AL, Felts JM (1972) Dispersal of rabbit lung into individual viable cells: a new model for the study of lung metabolism. Science 178:1209–1210

    PubMed  CAS  Google Scholar 

  • Gould VE, Smuckler EA (1971) Alveolar injury in acute carbon tetrachloride intoxication. Arch Intern Med 128:109–117

    PubMed  CAS  Google Scholar 

  • Gram TE (1973) Comparative aspects of mixed function oxidation by lung and liver of rabbits. Drug Metab Rev 2:1–32

    PubMed  CAS  Google Scholar 

  • Gram TE (1980) The metabolism of xenobiotics by mammalian lung in extrahepatic metabolism of drugs and other foreign compounds. In: Gram TE (ed) Extrahepatic metabolism of drugs and other foreign compounds. SP Medical and Scientific Books, Jamaica, pp 175–209

    Google Scholar 

  • Grasso P, Williams M, Hodgson R, Gangolli SD (1971) The histochemical distribution of aniline hydroxylase in rat tissues. Histochem J 3:117–126

    PubMed  CAS  Google Scholar 

  • Grover PL (1974) K-region epoxides of polycyclic hydrocarbons: formation and further metabolism by rat lung preparations. Biochem Pharmacol 23:333–343

    PubMed  CAS  Google Scholar 

  • Grover PL, Hewer A, Sims P (1973) K-region epoxides of polycyclic hydrocarbons: formation and further metabolism of benz[a]anthracene 5,6-oxide by human lung preparations. FEBS Lett 34:63–68

    PubMed  CAS  Google Scholar 

  • Grover PL, Hewer A, Sims P (1974) Metabolism of polycyclic hydrocarbons by rat lung preparations. Biochem Pharmacol 23:323–332

    PubMed  CAS  Google Scholar 

  • Guengerich FP (1977) Preparation and properties of highly purified cytochrome P-450 and NADPH cytochrome P-450 reductase from pulmonary microsomes of untreated rabbits. Mol Pharmacol 13:911–923

    PubMed  CAS  Google Scholar 

  • Guyton AC (1976) Pulmonary ventilation. In: Textbook of medical physiology, 5th edn. Saunders, Philadelphia, p 523

    Google Scholar 

  • Hanafy MSM, Bogan JA (1980) The covalent binding of 3-methylindole metabolites to bovine tissue. Life Sci 27:1225–1231

    PubMed  CAS  Google Scholar 

  • Harper C, Drew RT, Fouts JR (1973) Species differences in benzene Jhydroxylation to phenol by pulmonary and hepatic microsomes. Drug Metab Dispos 3:381–388

    Google Scholar 

  • Hesse S, Mezger M (1979) Involvement of phenolic metabolites in the irreversible protein-binding of aromatic hydrocarbons: reactive metabolites of 14C-naphthalene and 14C-1-naphthol formed by rat liver microsomes. Mol Pharmacol 16:667–675

    PubMed  CAS  Google Scholar 

  • Hilliker KS, Roth RA (1980) Prediction of mescaline clearance by rabbit lung and liver from enzyme kinetic data. Biochem Pharmacol 29:253–255

    PubMed  CAS  Google Scholar 

  • Hirai K-I, Witschi HP, Coté MG (1977) Electron microscopy of butylated hydroxytoluene-induced lung damage in mice. Exp Mol Pathol 27:295–308

    PubMed  CAS  Google Scholar 

  • Hollinger MA, Giri SN, Alley M, Budd E, Hwang F (1974) Tissue distribution and binding of radioactivity from 14C-thiourea in the rat. Drug Metab Dispos 2:251–261

    Google Scholar 

  • Hollinger MA, Giri SN, Hwang F (1976) Binding of radioactivity from 14C-thiourea to rat lung protein. Drug Metab Dispos 4:119–123

    PubMed  CAS  Google Scholar 

  • Holt PG, Keast D (1973) Induction of aryl hydrocarbon hydroxylase in the lungs of mice in response to cigarette smoke. Experientia 29:1004

    PubMed  CAS  Google Scholar 

  • Hook GE, Bend JR, Hoel D, Fouts JR, Gram TE (1972) Preparation of lung microsomes and a comparison of the distribution of enzymes between subcellular fractions of rabbit lung and liver. J Pharmacol Exp Ther 182:474–490

    PubMed  CAS  Google Scholar 

  • Hsu IC, Allen JR, Chesney CF (1973) Identification and toxicological effects of dehydroretronecine, a metabolite of monocrotaline. Proc Soc Exp Biol Med 144:834–842

    PubMed  CAS  Google Scholar 

  • Huang TW, Carlson JR, Bray TM, Bradley BJ (1977) 3-methylindole-induced pulmonary injury in goats. Am J Pathol 87:647–666

    PubMed  CAS  Google Scholar 

  • Huberman E, Kuroki T, Marquart H, Selkirk JK, Heidelberger C, Grover PL, Sims P (1972) Transformation of hamster embryo cells by epoxides and other derivatives of polycyclic hydrocarbons. Cancer Res 32:1391–1396

    PubMed  CAS  Google Scholar 

  • Hulshoff A, Lubauvy WC, Kostenbauder HB (1978) The effect of some cigarette smoke constituents and other compounds on the metabolism of benzo[a]pyrene in rabbit lung 9,000 g supernatant. Xenobiotica 8:711–718

    PubMed  CAS  Google Scholar 

  • Hundley SG, Freudenthal RI (1977a) A comparison of benzo[a]pyrene metabolism by liver and lung microsomal enzymes from 3-methylcholanthrene-treated rhesus monkeys and rats. Cancer Res 37:3120–3125

    PubMed  CAS  Google Scholar 

  • Hundley SG, Freudenthal RI (1977b) High-pressure liquid chromatography analysis of benzo[a]pyrene meabolism by microsomal enzymes from rhesus liver and lung. Cancer Res 37:244–249

    PubMed  CAS  Google Scholar 

  • Ichihara K, Kusunose E, Kusunose M (1969) Microsomal hydroxylation of decane. Biochim Biophys Acta 176:713–719

    PubMed  CAS  Google Scholar 

  • Ichikawa Y, Yamano T, Fujishima H (1969) Relationships between the interconversion of cytochrome P-450 and P-420 and its activities in hydroxylations and demethylations by P-450 oxidase systems. Biochim Biophys Acta 171:32–46

    PubMed  CAS  Google Scholar 

  • Ilett KF, Stipp B, Menard RM, Reid WD, Gillette JR (1974) Studies on the mechanism of the lung toxicity of paraquat: comparison of tissue distribution and some biochemical parameters in rats and rabbits. Toxicol Appl Pharmacol 28:216–226

    PubMed  CAS  Google Scholar 

  • Imamura T, Hasegawa L (1984) Role of metabolic activation, covalent binding and glutathione depletion in pulmonary toxicity produced by an impurity of malathion. Toxicol Appl Pharmacol 72:476–483

    PubMed  CAS  Google Scholar 

  • Imamura T, Gandy J, Fukuto TR (1983) Selective inhibition of rat pulmonary mono-oxygenase by O,O,S-trimethyl phosphorothioate treatment. Biochem Pharmacol 32: 3191–3195

    PubMed  CAS  Google Scholar 

  • Jago MV, Edgar J A, Smith LW, Culvenor CC (1970) Metabolic conversion of heliotridine-based pyrrolidine alkaloids to dehydroheliotridine. Mol Pharmacol 6:402–407

    PubMed  CAS  Google Scholar 

  • Johannesen K, DePierre JW, Bergstrand A, Dallner G, Ernster L (1977) Preparation and characterization of total, rough, and smooth microsomes from the lungs of control and methyleholanthrene-treated rats. Biochim Biophys Acta 496:115–135

    PubMed  CAS  Google Scholar 

  • Johnson KJ, Fantone JC, Kaplan J, Ward PA (1981) In vivo damage of rat lungs by oxygen metabolites. J Clin Invest 67:983–993

    PubMed  CAS  Google Scholar 

  • Jones AW, Reeve NL (1978) Ultrastructural study of bleomycin-inducee pulmonary changes in mice. J Pathol 124:227–233

    PubMed  CAS  Google Scholar 

  • Jones KW, Holland JF, Foureman GL, Bend JR, Fouts JR (1983) Xenobiotic metabolism in Clara cells and alveolar type II cells isolated from lungs of rats treated with β-naphthoflavone. J Pharmacol Exp Ther 225:316–319

    PubMed  CAS  Google Scholar 

  • Kapitulnik J, Wislocki PG, Levin W, Yagi H, Jerina DM, Conney AH (1978) Tumorigenieity studies with diol-epoxides of benzo[a]pyrene which indicate that (±) trans-7β,8α-dihydroxy-9α-10α-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene is an ultimate carcinogen in newborn mice. Cancer Res 38:354–358

    PubMed  CAS  Google Scholar 

  • Kasper CB (1971) Biochemical distinctions between the nuclear and microsomal membranes from rat hepatocytes. J Biol Chem 246:577–581

    PubMed  CAS  Google Scholar 

  • Kehrer JP, Haschek WM, Witschi HP (1979) The influence of hyperoxia on the acute toxicity of paraquat and diquat. Drug Chem Toxicol 2:397–408

    PubMed  CAS  Google Scholar 

  • Kehrer JP, Witschi HP (1980) Effects of drug metabolism inhibitors on butylated hydroxytoluene-induced pulmonary toxicity in mice. Toxicol Appl Pharmacol 53:333–342

    PubMed  CAS  Google Scholar 

  • Kikkawa Y, Yoneda K, Smith F, Packard B, Suzuki K (1975) The type II epithelial cells of the lung. II. Chemical composition and phospholipid biosynthesis. Lab Invest 32:295–302

    PubMed  CAS  Google Scholar 

  • Krijgsheld KR, Lowe MC, Mimnaugh EG, Trash MA, Ginsburg E, Gram TE (1984) Selective damage to nonciliated bronchiolar epithelial cells in relation to impairment of pulmonary monooxygenase activities by 1,1-diehloroethylene in mice. Toxicol Appl Pharmacol 74:201–213

    PubMed  CAS  Google Scholar 

  • Kuenzig W, Tkaezevski V, Kamm J J, Conney AH, Burns J J (1977) The effect of ascorbic acid deficiency on extrahepatic microsomal metabolism of drugs and carcinogens in the guinea pig. J Pharmacol Exp Ther 201:527–533

    PubMed  CAS  Google Scholar 

  • Kuhn C (1976) The cells of the lung and their organelles. In: Crystal RG (ed) The biochemical basis of pulmonary function. Dekker, New York, pp 3–48

    Google Scholar 

  • Kuhn C (1978) Ultrastructure and cellular function in the distal lung. In: The lung. IAP Monograph, No. 19. Williams and Wilkins, Baltimore, pp 1–20

    Google Scholar 

  • Lee PW, Araau T, Neal RA (1980) Metabolism of α-naphthylthiourea by rat liver and lung microsomes. Toxicol Appl Pharmacol 53:164–173

    PubMed  CAS  Google Scholar 

  • Levin W, Buening MK, Wood AW, Chang RL, Kedzierski B, Thakker DR, Boyd DR, Gadaginamath GS, Armstrong RN, Yagi H, Karle JM, Slaga TJ, Jerina DM, Conney AH (1980) An enantiomeric interaction in the metabolism and tumorigenicity of (+) and (−) benzo[a]pyrene 7,8-oxide. J Biol Chem 255:9067–9074

    PubMed  CAS  Google Scholar 

  • Litterst CL, Mimnaugh EG, Reagan RL, Gram TE (1975a) Comparison of in vitro drug metabolism by lung, liver and kidney of several common laboratory species. Drug Metab Dispos 3:259–265

    PubMed  CAS  Google Scholar 

  • Litterst CL, Mimnaugh EG, Reagan RL, Gram TE (1975b) Drug metabolism by microsomes from extrahepatic organs of rat and rabbit prepared by calcium aggregation. Life Sci 17:813–818

    PubMed  CAS  Google Scholar 

  • Litterst CL, Mimnaugh EG, Gram TE (1977) Comparative alterations in extrahepatic drug metabolism by factors known to affect hepatic activity. Biochem Pharmacol 26:749–755

    PubMed  CAS  Google Scholar 

  • Lu AYH, Coon MJ (1968) Role of hemoprotein P-450 in fatty acid co-hydroxylation in a soluble enzyme system from liver microsomes. J Biol Chem 243:1331–1332

    PubMed  CAS  Google Scholar 

  • Mahvi D, Bank H, Harley R (1977) Morphology of a naphthalene-induced bronchiolar lesion. Am J Pathol 86:559–572

    CAS  Google Scholar 

  • Malkinson AM (1979) Prevention of butylated hydroxytoluene-induced lung damage in mice by cedar terpene administration. Toxicol Appl Pharmacol 49:551–560

    PubMed  CAS  Google Scholar 

  • Marcotte J, Witschi HP (1972) Induction of pulmonary aryl hydrocarbon hydroxylase by marijuana. Res Commun Chem Pathol Pharmacol 4:561–568

    PubMed  CAS  Google Scholar 

  • Marino A, Mitchell JT (1972) Lung damage in mice following intraperitoneal injection of butylated hydroxytoluene. Proc Soc Exp Biol Med 140:122–125

    PubMed  CAS  Google Scholar 

  • Mason HS (1965) Oxidases. Annu Rev Biochem 34:595–634

    PubMed  CAS  Google Scholar 

  • Mason RP, Holtzman JL (1975) The role of catalytic superoxide formation in the oxygen inhibition of nitroreductase. Biochem Biophys Res Commun 67:1267–1274

    PubMed  CAS  Google Scholar 

  • Matsubara T, Tochino Y (1971) Electron transport systems of lung microsomes and their physiological functions. I. Intracellular distribution of oxidative enzymes in lung cells. J Biochem (Tokyo) 70:981–991

    CAS  Google Scholar 

  • Matsubara T, Prough RA, Burke MD, Estabrook RW (1974) The preparation of microsomal fractions of rodent respiratory tract and their characterization. Cancer Res 34:2196–2203

    PubMed  CAS  Google Scholar 

  • Mattocks AR (1972) Toxicity and metabolism of Senecio alkaloids. In: Harborne JB (ed) Phytochemical ecology. Academic, New York

    Google Scholar 

  • Mattocks AR, White INH (1971) The conversion of pyrrolidine alkaloids to N-oxides and to dihydropyrrolizidine derivatives by rat liver microsomes in vitro. Chem Biol Interact 3:383–391

    PubMed  CAS  Google Scholar 

  • McLemore TL, Martin RR, Bushee DL, Richie RC, Springer RR, Toppell KL, Cantrell ET (1977) Aryl hydrocarbon hydroxylase activity in pulmonary macrophages and lymphocytes from lung cancer and noncancer patients. Cancer Res 37:1175–1181

    PubMed  CAS  Google Scholar 

  • McManus ME, Boobis AR, Pacifici GM, Frempang RY, Brodie MJ, Kahn GC, Whyte C, Davies DS (1980) Xenobiotic metabolism in the human lung. Life Sci 26:481–487

    PubMed  CAS  Google Scholar 

  • Miranda CL, Mukhtar H, Bend JR, Chhabra RS (1979) Effects of vitamin A deficiency on hepatic and extrahepatic mixed function oxidase and epoxide metabolizing enzymes in guinea pig and rabbit. Biochem Pharmacol 28:2713–2716

    PubMed  CAS  Google Scholar 

  • Morgan TE (1971) Pulmonary surfactant. N Engl J Med 284:1185–1193

    PubMed  CAS  Google Scholar 

  • Nakagawa Y, Hiraga K, Suga T (1979) Biological fate of butylated hydroxytoluene (BHT): binding in vitro of BHT to liver microsomes. Chem Pharm Bull (Tokyo) 27:480–485

    CAS  Google Scholar 

  • Nakazawa K, Costa E (1971) Metabolism of Δ 9 tetrahydrocannabinol by lung and liver homogenates of rats treated with methylcholanthrene. Nature 234:48–49

    PubMed  CAS  Google Scholar 

  • Okamoto T, Chan P-C, So BT (1972) Effect of tobacco, marijuana, and benzo[a]pyrene on aryl hydrocarbon hydroxylase in hamster lung. Life Sci 11:733–741

    CAS  Google Scholar 

  • Oppelt WW, Zange M, Ross WE, Remmer H (1970) Comparison of microsomal drug hydroxylation in lung and liver of various species. Res Commun Chem Pathol Pharmacol 1:43–56

    PubMed  CAS  Google Scholar 

  • Paine AJ (1978) Excited states of oxygen in biology: their possible involvement in cytochrome P-450 linked oxidations as well as the induction of the P-450 system by many diverse compounds. Biochem Pharmacol 27:1805–1813

    PubMed  CAS  Google Scholar 

  • Patel JM, Harper C, Drew RT (1978) The biotransformation of p-xylene to a toxic aldehyde. Drug Metab Dispos 6:368–374

    PubMed  CAS  Google Scholar 

  • Philpot RM, Anderson MW, Eling TE (1977) Uptake, accumulation, and metabolism of chemicals by the lung. In: Bakhle YS, Vane JR (eds) Metabolic functions of the lung. Marcel Dekker, New York, pp 123–171

    Google Scholar 

  • Picciano P, Rosenbaum RM (1978) The type I alveolar lining cells of the mammalian lung. I. Isolation and enrichment from dissociated adult rabbit lung. Am J Pathol 90:99–122

    PubMed  CAS  Google Scholar 

  • Plopper CG, Mariassy AT, Hill LH (1980) Ultrastructure of the nonciliated bronchiolar epithelial (Clara) cell of mammalian lung. I. A comparison of rabbit, guinea pig, rat, hamster, and mouse. Exp Lung Res 1:139–154

    PubMed  CAS  Google Scholar 

  • Poland AP, Glover E, Robinson JR, Nebert DW (1974) Genetic expression of aryl hydrocarbon hydroxylase activity. J Biol Chem 249:5599–5606

    PubMed  CAS  Google Scholar 

  • Prough RA, Burke MD (1975) The role of NADPH cytochrome c reductase in microsomal hydroxylation reactions. Arch Biochem Biophys 170:160–168

    PubMed  CAS  Google Scholar 

  • Ravindranath V, Burka LT, Boyd MR (1984) Reactive metabolites from the bioactivation of toxic methylfurans. Science 224:884–886

    PubMed  CAS  Google Scholar 

  • Recknagel RO, Glende EA (1973) Carbon tetrachloride hepatotoxicity: an example of lethal cleavage. CRC Crit Rev Toxicol 2:263–297

    Google Scholar 

  • Reid WD, Glick JM, Krishna G (1972) Metabolism of foreign compounds by alveolar macrophages of rabbits. Biochem Biophys Res Commun 49:626–634

    PubMed  CAS  Google Scholar 

  • Reid WD, Ilett KF, Glick JM, Krishna G (1973) Metabolism and binding of aromatic hydrocarbons in the lung: relationship to experimental bronchiolar necrosis. Am Rev Respir Dis 107:539–551

    PubMed  CAS  Google Scholar 

  • Reiss OK (1966) Studies of lung metabolism. I. Isolation and properties of subcellular fractions from rabbit lung. J Cell Biol 30:45–57

    PubMed  CAS  Google Scholar 

  • Rhodes ML, Zavala DC, Brown D (1976) Hypoxic protection in paraquat poisoning. Lab Invest 35:496–500

    PubMed  CAS  Google Scholar 

  • Richter CP (1945) The development and use of alphanaphthylthiourea (ANTU) as a rat poison. JAMA 129:927–930

    CAS  Google Scholar 

  • Riehter CP (1946) Biological factors involved in poisoning rats with alphanaphthylthiourea. Proc Soc Exp Biol Med 63:364–370

    Google Scholar 

  • Richter CP (1952) The physiology and cytology of pulmonary edema and pleural effusion produced in rats by alphanaphthylthiourea (ANTU). J Thorac Cardiosvase Surg 23:66–72

    CAS  Google Scholar 

  • Robertson B, Enhorning G, Ivemark B, Malmquist J, Modee J (1971) Experimental respiratory distress induced by paraquat. J Pathol 103:239–244

    PubMed  CAS  Google Scholar 

  • Roth RA, Wiersma DA (1980) Role of the lung in total body clearance of circulating drugs. Clin Pharmacokinet 4:355–367

    Google Scholar 

  • Sasame HA, Boyd MR (1979) Superoxide and hydrogen peroxide production and NADPH oxidation stimulated by nitrofurantoin in lung microsomes: possible implications for toxicity. Life Sci 24:1091–1096

    PubMed  CAS  Google Scholar 

  • Sausville EA, Peisach J, Horwitz SB (1976) A role for ferrous ion and oxygen in the degradation of DNA by bleomycin. Biochem Biophys Res Commun 73:814–822

    PubMed  CAS  Google Scholar 

  • Schoental R (1968) Toxicology and carcinogenic action of pyrrolizidine alkaloids. Cancer Res 28:2237–2246

    PubMed  CAS  Google Scholar 

  • Seifried HE, Birkett DJ, Levin W, Lu AYH, Conney AH, Jerina DM (1977) Metabolism of benzo[a]pyrene: effect of 3-methylcholanthrene pretreatment on metabolism by microsomes from lungs of genetically “responsive” and “nonresponsive” mice. Arch Biochem Biophys 178:256–263

    PubMed  CAS  Google Scholar 

  • Selkirk JK, Croy RG, Gelboin HV (1974a) Benzo[a]pyrene metabolites: efficient and rapid separation by high-pressure liquid chromatography. Science 184:169–171

    PubMed  CAS  Google Scholar 

  • Selkirk JK, Croy RG, Roller PP, Gelboin HY (1974b) High pressure liquid chromatographic analysis of benzo[a]pyrene metabolism and covalent binding and the mechanism of action of 7,8-benzoflavone and l,2-epoxy-3,3,3-trichloropropane. Cancer Res 34:3474–3480

    PubMed  CAS  Google Scholar 

  • Serabjit-Singh CJ, Wolf CR, Philpot RM (1979) The rabbit pulmonary monooxygenase system: immunochemical and biochemical characterization of enzyme components. J Biol Chem 254:9901–9907

    PubMed  CAS  Google Scholar 

  • Serabjit-Singh CJ, Wolf CR, Philpot RM, Plopper CG (1980) Cytochrome P-450: localize ation in rabbit lung. Science 207:1469–1470

    PubMed  CAS  Google Scholar 

  • Sevanian A, Kaplan SA, Barrett CT (1981) Phospholipid synthesis in fetal lung organotypic cultures and isolated type II pneumocytes. Biochim Biophys Acta 664:498–512

    PubMed  CAS  Google Scholar 

  • Sikic BI, Mimnaugh EG, Litterst CL, Gram TE (1977) The effects of ascorbic acid depletion and repletion on pulmonary, renal, and hepatic drug metabolism in the guinea pig. Arch Biochem Biophys 179:663–671

    PubMed  CAS  Google Scholar 

  • Sikic BI, Young DM, Mimnaugh EG, Gram TE (1978) Quantification of bleomycin pulmonary toxicity in mice by changes in lung hydroxyproline content and morphometry histopathology. Cancer Res 38:787–792

    PubMed  CAS  Google Scholar 

  • Sims P, Grover PL, Swaisland A, Pal K, Hewer A (1974) Metabolic activation of benzo[a]-pyrene proceeds by a diol-epoxide. Nature 252:326–328

    PubMed  CAS  Google Scholar 

  • Sipal Z, Ablenius T, Bergstrand A, Rodriguez L, Jakobsson SW (1979) Oxidative biotransformation of benzo[a]pyrene by human lung microsomal fractions prepared from surgical specimens. Xenobiotica 9:633–645

    PubMed  CAS  Google Scholar 

  • Slaga TJ, Bracken WJ, Gleason G, Levin W, Yagi H, Jerina DM, Conney AH (1979) Marked differences in the skin tumor-initiating activities of the optical enantiomers of the diastereomeric benzo[a]pyrene 7,8-diol-9,10-epoxides. Cancer Res 39:67–71

    PubMed  CAS  Google Scholar 

  • Slaughter SR, Wolf CR, Marciniszyn JP, Philpot RM (1981) The rabbit pulmonary monooxygenase system: partial structural characterization of the cytochrome P-450 components and comparison to the hepatic cytochrome P-450. J Biol Chem 256:2499–2503

    PubMed  CAS  Google Scholar 

  • Smith BR, Maguire JH, Ball LM, Bend JR (1978) Pulmonary metabolism of epoxides. Fed Proc 37:2480–2484

    PubMed  CAS  Google Scholar 

  • Smith LL, Rose MS, Wyatt I (1979) The pathology and biochemistry of paraquat. Ciba Found Symp 65:321–336

    CAS  Google Scholar 

  • Smith P, Heath D (1974) The ultrastructure and time sequence of the early stages of paraquat lung in rats. J Pathol 114:177–184

    PubMed  CAS  Google Scholar 

  • Smith P, Heath D (1976) Paraquat. CRC Crit Rev Toxicol 4:411–445

    PubMed  CAS  Google Scholar 

  • Smith P, Heath D, Kay JK (1974) The pathogenesis and structure of paraquat induced pulmonary fibrosis in rats. J Pathol 114:57–67

    PubMed  CAS  Google Scholar 

  • Snyder R, Remmer H (1979) Classes of hepatic microsomal mixed function oxidase inducers. Pharmacol Ther 7:203–244

    PubMed  CAS  Google Scholar 

  • Sorokin SP (1970) The cells of the lungs. In: Nettesheim P, Hanna MG, Deatherage JW (eds) Morphology of experimental respiratory carcinogenesis. U.S. Atomic Energy Commission, pp 3–43

    Google Scholar 

  • Sovijarvi ARA, Lemola M, Stenius B, Adanpaan-Heikkila J (1977) Nitrofurantoin induced acute, subacute, and chronic pulmonary reactions. Scand J Respir Dis 58:41–50

    PubMed  CAS  Google Scholar 

  • Sunderman FW, Leibman KC (1970) Nickel carbonyl inhibition of induction of aminopyrine demethylase activity in liver and lung. Cancer Res 30:1645–1650

    PubMed  CAS  Google Scholar 

  • Teel RW, Douglas WHJ (1980) Aryl hydrocarbon hydroxylase activity in type II alveolar lung cells. Experientia 36:107

    PubMed  CAS  Google Scholar 

  • Tierney DF (1974) Lung metabolism and biochemistry. Annu Rev Physiol 36:209–231

    PubMed  CAS  Google Scholar 

  • Tong SS, Hirokata Y, Trash MA, Mimnaugh EG, Ginsburg E, Lowe MC, Gram TE (1981) Clara cell damage and inhibition of pulmonary mixed-function oxidase activity by naphthalene. Biochem Biophys Res Commun 100:944–950

    PubMed  CAS  Google Scholar 

  • Trush MA, Mimnaugh EG, Ginsburg E, Gram TE (1981) In vitro stimulation by paraquat of reactive oxygen-mediated lipid peroxidation in rat lung microsomes. Toxicol Appl Pharmacol 60:279–286

    PubMed  CAS  Google Scholar 

  • Trush MA, Mimnaugh EG, Ginsburg E, Gram TE (1982a) Studies on the interaction of bleomycin A2 with rat lung microsomes. I. Characterization of factors which influence bleomycin-mediated DNA chain breakage. J Pharmacol Exp Ther 221:152–158

    PubMed  CAS  Google Scholar 

  • Trush MA, Mimnaugh EG, Ginsburg E, Gram TE (1982b) Studies on the interaction of bleomycin A2 with rat lung microsomes. II. Involvement of adventitious iron and reactive oxygen in bleomycin-mediated DNA chain breakage. J Pharmacol Exp Ther 221:159–165

    PubMed  CAS  Google Scholar 

  • Uehleke H (1968) Extrahepatic microsomal drug metabolism. In: Sensitization to drugs. Excerpta Medical International Congress Series No. 181, pp 94–100

    Google Scholar 

  • Ueng T-H, Alvares AP (1981) Selective loss of pulmonary cytochrome P-4501 in rabbits pretreated with polychlorinated biphenyls. J Biol Chem 256:7536–7542

    PubMed  CAS  Google Scholar 

  • Valdivia E, Sonnad J (1966) Fatty change of the granular pneumocyte in CC14 intoxication. Arch Pathol 81:514–519

    PubMed  CAS  Google Scholar 

  • Van Cantfort J, Gielen J (1975) Organ specificity of aryl hydrocarbon hydroxylase induction by cigarette smoke in rats and mice. Biochem Pharmacol 24:1253–1256

    PubMed  Google Scholar 

  • Vijeyaratnam GS, Corrin B (1971) Experimental paraquat poisoning: a histological and electron-optical study of the changes in the lung. J Pathol 103:123–129

    PubMed  CAS  Google Scholar 

  • Warren DL, Brown DL, Buckpitt AR (1982) Evidence for cytochrome P-450 mediated metabolism in the bronchiolar damage by naphthalene. Chem Biol Interact 40:287–303

    PubMed  CAS  Google Scholar 

  • Warren PM, Bellward GD (1978) Induction of aryl hydrocarbon hydroxylase by 3-methyl-eholanthrene in liver, lung, and kidney of gonadectomized and sham-operated Wistar rats. Biochem Pharmacol 27:2537–2541

    PubMed  CAS  Google Scholar 

  • Watanabe M, Konno K, Sato H (1978) Properties of aryl hydrocarbon (benzo[a]pyrene) hydroxylase in lung microsomes of mice. Gann 69:1–8

    PubMed  CAS  Google Scholar 

  • Wattenberg LW, Leong JL (1962) Histochemical demonstration of reduced pyridine nu: cleotide dependent poly cyclic hydrocarbon metabolizing systems. J Histochem Cytochem 10:412–420

    CAS  Google Scholar 

  • Wattenberg LW, Leong JL, Galbraith AR (1967) Induction of increased benzpyrene hydroxylase activity in pulmonary tissue in vitro. Proc Soc Exp Biol Med 127:467–469

    Google Scholar 

  • Wattenberg LW, Page MA, Leong JL (1968a) Induction of increased benzpyrene hydroxylase activity by flavones and related compounds. Cancer Res 28:934–937

    PubMed  CAS  Google Scholar 

  • Wattenberg LW, Page MA, Leong JL (1968b) Induction of increased benzpyrene hydroxylase activity by 2-phenylbenzothiazoles and related compounds. Cancer Res 28:2539–2544

    PubMed  CAS  Google Scholar 

  • Welch RM, Loh A, Conney AH (1971) Cigarette smoke: stimulatory effect on metabolism of 3,4-benzpyrene by enzymes in rat lung. Life Sci 10:215–221

    CAS  Google Scholar 

  • Welch RM, Cavallito J, Loh A (1972) Effect of exposure to cigarette smoke on the metabolism of benzo[a]pyrene and acetophenetidin by lung and intestine of rats. Toxicol Appl Pharmacol 23:749–758

    PubMed  CAS  Google Scholar 

  • Weiss RM, Muggia FM (1980) Cytotoxic drug-induced pulmonary disease: update 1980. Am J Med 68:259–266

    PubMed  CAS  Google Scholar 

  • Wiebel F J, Lentz JC, Diamond L, Gelboin HY (1971) Aryl hydrocarbon (benzo[a]pyrene) hydroxylase in microsomes from rat tissues: differential inhibition and stimulation by benzoflavones and organic solvents. Arch Biochem Biophys 144:78–86

    PubMed  CAS  Google Scholar 

  • Wiebel F J, Leutz JC, Gelboin HV (1973) Aryl hydrocarbon (benzo[a]pyrene) hydroxylase: inducible in extrahepatic tissues of mouse strains not inducible in liver. Arch Biochem Biophys 154:292–294

    PubMed  CAS  Google Scholar 

  • Willson JKV (1978) Pulmonary toxicity of antineoplastic drugs. Cancer Treat Rep 62:2003–2008

    PubMed  CAS  Google Scholar 

  • Witschi HP (1976) Proliferation of type II alveolar cells: a review of common responses in toxic lung injury. Toxicology 5:267–277

    CAS  Google Scholar 

  • Witschi HP, Saheb W (1974) Stimulation of DNA synthesis in mouse lung following intraperitoneal injection of butylated hydroxytoluene. Proc Soc Exp Biol Med 147:690–693

    PubMed  CAS  Google Scholar 

  • Witschi HP, St-Francois B (1972) Enhanced activity of benzpyrene hydroxylase in rat liver and lung after acute cannabis administration. Toxicol Appl Pharmacol 23:165–168

    PubMed  CAS  Google Scholar 

  • Witschi HP, Kacew S, Hirai K-I, Côté MG (1977) In vivo oxidation of reduced nicotinamide-adenine dinucleotide phosphate by paraquat and diquat in rat lung. Chem Biol Interact 19:143–160

    PubMed  CAS  Google Scholar 

  • Wolf CR, Szutowski MM, Ball LM, Philpot RM (1978) The rabbit pulmonary monooxygenase system: characteristics and activities of two forms of pulmonary cytochrome P-450. Chem Biol Interact 21:29–43

    PubMed  CAS  Google Scholar 

  • Wolf CR, Smith BR, Ball LM, Serabjit-Singh C, Bend JR, Philpot RM (1979) The rabbit pulmonary monooxygenase system: catalytic differences between two purified forms of cytochrome P-450 in the metabolism of benzo[a]pyrene. J Biol Chem 254:3658–3663

    PubMed  CAS  Google Scholar 

  • Yang SK, Selkirk JK, Plotkin EV, Gelboin HV (1975) Kinetic analysis of the metabolism of benzo[a]pyrene to phenols, dihydrodiols, and quinones by high pressure chromatography compared to analysis by aryl hydrocarbon hydroxylase assay, and the effect of enzyme induction. Cancer Res 35:3642–3650

    PubMed  CAS  Google Scholar 

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  1. T. E. Gram
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Editors and Affiliations

  1. Toxicology, Biology Division, Oak Ridge National Laboratory, P.O. Box Y, 37831, Oak Ridge, TN, USA

    Hanspeter Witschi M.D. (Section Head) (Section Head)

  2. Department of Environmental Science and Physiology, Harvard University School of Public Health, 665 Huntington Ave., 02115, Boston, MA, USA

    Joseph D. Brain S.D. in Hyg. (Professor of Physiology, Director, Respiratory Biology Program) (Professor of Physiology, Director, Respiratory Biology Program)

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Gram, T.E. (1985). The Pulmonary Mixed-Function Oxidase System. In: Witschi, H., Brain, J.D. (eds) Toxicology of Inhaled Materials. Handbook of Experimental Pharmacology, vol 75. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-69521-6_14

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