63
Views
215
CrossRef citations to date
0
Altmetric
Research Article

Biochemical Mechanisms in Chemical-Induced Lung Injury: Roles of Metabolic Activation

&
Pages 103-176 | Published online: 26 Sep 2008

References

  • Miller E. C., Miller J. A. Mechanisms of chemical carcinogenesis: nature of proximate carcinogens and interactions with macromolecules. Pharmacol. Rev. 1966; 18: 805
  • Miller J. A. Carcinogenesis by chemicals: an overview — G. H. A. Clowes Memorial Lecture. Cancer Res. 1970; 30: 559
  • Miller E. C. Some current perspectives on chemical carcinogenesis in humans and experimental animals: presidential address. Cancer Res. 1978; 38: 1479
  • Magee P. N. Activation and inactivation of chemical carcinogens and mutagens in the mammal. Essays Biochem. 1974; 10: 105
  • Rechnagel R. O., Glende E. A. Carbon tetrachloride hepatotoxicity: an example of lethal cleavage. CRC Crit. Rev. Toxicol. 1973; 2: 263
  • Gillette J. R., Mitchell J. R., Brodie B. B. Biochemical mechanisms of drug toxicity. Annu. Rev. Pharmacol 1974; 14: 271
  • Gilette J. R. A perspective on the role of chemically reactive metabolites of foreign compounds in toxicity. 1. Correlation of changes in covalent binding of reactive metabolites with changes in the incidence and severity of toxicity. Biochem. Pharmacol. 1974; 23: 2785
  • Gillette J. R. A perspective on the role of chemically reactive metabolites of foreign compounds in toxicity. II. Alterations in the kinetics of covalent binding. Biochem. Pharmacol. 1974; 23: 2927
  • Nelson S. D., Boyd M. R., Mitchell J. R. Role of metabolic activation in chemical-induced tissue injury. Drug Metabolism Concepts, D. M. Jerina. American Chemical Society, Washington, DC 1977, chap. 8
  • Boyd M. R. 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. 1976; 16: 127
  • Weisburger J. H., Weisburger E. K. Biochemical formation and pharmacological, toxicological and pathological properties of hydroxylamines and hydroxamic acids. Pharmacol. Rev. 1973; 25: 1
  • Judah J. D., McLean A. E., McLean E. K. Biochemical mechanism of liver injury. Am. J. Med. 1970; 49: 609
  • Bonse G., Henschler D. Chemical reactivity, biotransformation, and toxicity of polychlorinated aliphatic compounds. CRC Crit. Rev. Toxicol. 1976; 4: 395
  • Boyd M. R. Biochemical mechanisms in pulmonary toxicity of furan derivatives. Reviews in Biochemical Toxicology, E. Hodgson, J. Bend, R. Philipot. Elsevier/North Holland, New York 1980; 141
  • Boyd M. R., Dutcher J. S., Buckpitt A. R. Jones, R. B., and Statham, C. N., Role of metabolic activation in extrahepatic target organ alklyation and cytotoxicity by 4-ipomeanol, a furan derivative from moldy sweet potatoes; possible implications for carcinogenesis. Naturally-Occurring Carcinogens — Mutagens and Modulators of Carcinogenesis, E. Miller, J. Miller, I. Hirono, T. Sugimura, S. Takayama. University Park Press, Baltimore 1979; 35
  • Boyd M. R., Buckpitt A. R., Jones R. B., Statham C. N., Longo N. S. Metabolic activation of toxins in extrahepatic target organs and target cells. The Scientific Basis of Toxicity Assessment, H. R. Witschi. Elsevier/North Holland, New York 1980; 141
  • Boyd M. R. Effects of inducers and inhibitors on drug-metabolizing enzymes and drug toxicity in extrahepatic tissues. Environmental Chemicals, Enzyme Function and Human Disease. Excerpta Medica, Amsterdam, Ciba Foundation Symposium No. 76, in press
  • Witschi H., Côté M. G. Primary pulmonary responses to toxic agents. CRC Crit. Rev. Toxicol. 1977; 5: 23
  • Hook G. E. R., Bend J. R. Pulmonary metabolism of xenobiotics. Life Sci. 1976; 18: 279
  • Gram T. E. Comparative aspects of mixed function oxidation by lung and liver of rabbits. Drug Metab. Rev. 1973; 2: 1
  • Remmer H. Pulmonary drug-metabolizing enzymes. Lung Metabolism, A. F. Junod, R. De-Haller. Academic Press, New York 1975; 133
  • Junod A. F. Uptake, release, and metabolism of drugs in the lungs. Pharmac. Ther. B 1976; 2: 511
  • Junod A. F. Mechanisms of drug accumulation in the lung. Lung Metabolism, A. F. Junod, R. DeHaller. Academic Press, New York 1975; 219
  • Philpot R. M., Anderson M. W., Eling T. M. Uptake, accumulation, and metabolism of chemicals by the lung. Metabolic Functions of the Lung, Y. S. Bakhle, J. R. Vane. Marcel Dekker, New York 1977, chap. 5
  • Brown E. A. B. The localization, metabolism, and effects of drugs and toxicants in lung. Drug Metab. Rev. 1974; 3: 33
  • Alabaster V. A. Inactivation of endogenous amines in the lungs. Metabolic Functions of the Lung, Y. S. Bakhle, J. R. Vane. Marcel Dekker, New York 1977, chap. 1
  • Wilson B. J., Yang D. T. C., Boyd M. R. Toxicity of mold-damaged sweet potatoes (Ipomoea batatas). Nature (London) 1970; 227: 521
  • Wilson B. J., Boyd M. R., Harris T. M., Yang D. T. C. Lung edema factor from moldy sweet potatoes (. Ipomoea batatas), Nature (London) 1971; 231: 52
  • Boyd M. R., Harris T. M., Wilson B. J. Confirmation by chemical synthesis of the structure of 4-ipomeanol, a lung-toxic metabolite of the sweet potato (. Ipomea batatas). Nature (London) New Biol. 1972; 236: 158
  • Boyd M. R., Wilson B. J. Isolation and characterization of 4-ipomeanol, a lung-toxic furano-terpenoid produced by sweet potatoes. J. Agric. Food Chem. 1972; 20: 428
  • Wilson B. J., Boyd M. R. Sweet potato toxins stimulated byFusarium solani and Ceratocystis fimbriata. Mycotoxins, I. F. H. Purchase. Elsevier, New York 1974, chap. 15
  • Boyd M. R., Burka L. T., Harris T. M., Wilson B. J. Lung-toxic furanoterpenoids produced by sweet potatoes (Ipomoea batatas) following microbial infection. Biochim. Biophys. Acta 1974; 337: 184
  • Peckham J. C., Mitchell F. E., Jones O. H., Jr., Doupnik B. Atypical interstitial pneumonia in cattle fed moldy sweet potatoes. J. Am. Vet. Med. Assoc. 1972; 160: 169
  • Doster A. R., Mitchell F. E., Farrell R. L., Wilson B. J. Effects of 4-ipomeanol, a product from mold-damaged sweet potatoes, on the bovine lung. Vet. Pathol. 1978; 15: 367
  • Boyd M. R., Wilson B. J. Preparative and analytical gas chromatography of ipomeamarone, a toxic metabolite of sweet potatoes (. Ipomea batatas), J. Agric. Food Chem. 1971; 19: 547
  • Dutcher J. S., Boyd M. R. Species and strain differences in tissue alkylation and toxicity by 4-ipomeanol: predictive value of covalent binding in the study of target organ toxicity. Toxicol. Appl. Pharmacol. 1978; 45: 267
  • Dutcher J. S., Boyd M. R. 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
  • Boyd M. R. Evidence for the Clara cell as a site of cytochrome P450-dependent mixed-function oxidase activity in lung. Nature (London) 1977; 269: 713
  • Boyd M. R., Burka L. T., Neal R. A., Wilson B. J., Holscher M. M. Role of covalent binding in the toxic mechanism of the lung-edemagenic agent, 4-ipomeanol. Fed. Proc. 1974; 33: 234
  • Boyd M. R., Burka L. T. In vivo studies on the relationship between target organ alkylation and the pulmonary toxicity of a chemically reactive metabolite of 4-ipomeanol. J. Pharmacol. Exp. Ther. 1978; 207: 687
  • Boyd M. R., Dutcher J. S. Role of renal metabolism in the pathogenesis of renal cortical necrosis by 4-ipomeanol in the mouse. Toxicol. Appl. Pharmacol. 1978; 45: 229
  • Jones R., Allegra C, Boyd M. Predictive value of covalent binding in target organ toxicity: age-related differences in target organ alkylation and toxicity by 4-ipomeanol. Toxicol. Appl. Pharmacol. 1979; 48: A129
  • Longo N. S., Boyd M. R. Sex differences in renal alkylation and toxicity by 4-ipomeanol in the mouse. Toxicol. Appl. Pharmacol., in press
  • Buckpitt A. R., Boyd M. R. Xenobiotic metabolism in birds, species lacking pulmonary Clara cells. Pharmacologist 1978; 20: 181
  • Fedde M. R. Respiration. Avian Physiology, P. D. Sturkie. Springer-Verlag, New York 1976, chap. 6
  • Boyd M. R., Buckpitt A. R. unpublished results
  • Boyd M. R., Burka L. T., Wilson B. J., Sastry B. V. R. Distribution and excretion of radioactivity in the rat after administratin of the lung-edemagenic toxin, 4-ipomeanol-14C. Toxicol. Appl. Pharmacol. 1974; 29: 132
  • Boyd M. R., Burka L. T., Wilson B. J. Distribution, excretion and binding of radioactivity in the rat after intraperitoneal administration of the lung-toxic furan, 4-ipomeanol-14C. Toxicol. Appl. Pharmacol. 1975; 32: 147
  • Staub N. C. Pulmonary edema. Physiol. Rev. 1974; 54: 678
  • Boyd M. R., Burka L. T., Wilson B. J., Sasame H. A. In vitro studies on the metabolic activation of the pulmonary toxin, 4-ipomeanol, by rat lung and liver microsomes. J. Pharmacol. Exp. Ther. 1978; 207: 677
  • Sasame H. A., Boyd M. R. Possible role of cytochrome bs as a rate-limiting factor in metabolic activation of 4-ipomeanol by lung microsomes. Fed. Proc. 1978; 37: 464
  • Sasame H. A., Gillette J. R., Boyd M. R. Effects of anti-NADPH-cytochromec reductase and anti-cytochrome bs antibodies on the hepatic and pulmonary microsomal metabolism and covalent binding of the pulmonary toxin, 4-ipomeanol. Biochem. Biophys. Res. Commun. 1978; 84: 389
  • Sasame H. A., Boyd M. R. Paradoxical effects of cobaltous chloride and salts of other divalent metals on tissue levels of reduced glutathione and microsomal mixed-function oxidase components. J. Pharmacol. Exp. Ther. 1978; 205: 718
  • Guengerich F. P. Separation and purification of multiple forms of cytochrome P-450. Activities of different forms of cytochrome P-450 towards several compounds of environmental interest. J. Biol. Chem. 1977; 252: 3970
  • Guengerich F. P. Preparation and properties of highly purified cytochrome P-450 and NADPH-cytochrome P-450 reductase from pulmonary microsomes of untreated rabbits. Mol. Pharmacol. 1977; 13: 911
  • Schenkman J. B., Jansson I., Robie-Suh K. M. The many roles of cytochrome bs in hepatic microsomes. Life Sci. 1976; 19: 611
  • Sasame H. A., Thorgiersson S. S., Mitchell J. R., Gillette J. R. The possible involvement of cytochrome bs in the oxidation of lauric acid by microsomes from kidney cortex and liver of rats. Life Sci. 1974; 14: 35
  • Gillette J. R., Davis D. C., Sasame H. A. Cytochrome P-450 and its role in drug metabolism. Annu. Rev. Pharmacol. 1972; 12: 57
  • Boyd M. R. Hepatotoxicity produced by the lung-toxic furanoterpenoid, 4-ipomeanol, after mixed-function oxidase induction: reversal of target organ for toxicity and covalent binding in rats pre-treated with 3-methyl-cholanthrene. Toxicol. Appl. Pharmacol. 1975; 33: 132
  • Boyd M., Statham C., Stiko A., Mitchell J., Jones R. Possible protective role of glutathione in pulmonary toxicity by 4-ipomeanol. Toxicol. Appl. Pharmacol. 1979; 48: A66
  • Buckpitt A. R., Boyd M. R. Determination of electrophilic metabolites produced during microsomal metabolism of 4-ipomeanol by high-pressure anion exchange chromatography of the glutathione adducts. Fed. Proc. 1979; 38: 692
  • Statham C. N., Boyd M. R. Distribution and metabolism of the pulmonary toxin 4-ipomeanol, in control and diethyl maleate-treated rats. Pharmacologist 1979; 21: 195
  • Nelson S. D., Buckpitt A. R., Boyd M. R. Unpublished results
  • Mitchell J. R., Jollow D. J., Potter W. Z., Gillette J. R., Brodie B. B. Acetaminophen-induced hepatic necrosis. IV. Protective role of glutathione. J. Pharmacol. Exp. Ther. 1973; 187: 211
  • Jollow D. J., Mitchell J. R., Zampaglione N., Gillette J. R. Bromobenzene induced liver necrosis. Protective role of glutathione and evidence for 3, 4-bromobenzene oxide as the hepatotoxic intermediate. Pharmacology 1974; 11: 151
  • Mitchell J. R., Boyd M. R. Dose thresholds, host susceptibility, and Pharmacokinetic considerations in the evaluation of toxicity from chemically reactive metabolites. Proc. 1st Int. Congr. Toxicology, G. L. Plaa, W. A. M. Duncan. Academic Press, New York 1978; 169
  • Boyd M. R., Wilson B. J., Sastry B. V. R. Acute toxicity and development of tolerance to 4-ipomeanol, a lung edemagenic toxin from sweet potatoes (Ipomoea batatas). 5th Int. Congr. Pharmacol., San Francisco, July 23 to 28, 1972, 28
  • Boyd M. R., Burka L. T., Osborne B. A., Wilson B. J. Studies on the mechanism of tolerance development to the pulmonary toxicity of 4-ipomeanol. Toxicol. Appl. Pharmacol. 1975; 33: 135
  • Fairchild E. J. Tolerance mechanisms. Determinants of lung responses to injurious agents. Arch. Environ. Health 1967; 14: 111
  • Swenson D. H., Miller E. C., Miller J. A. Aflatoxin Bl-2–3-oxide: evidence for its formation in rat liverin vivo and by human liver microsomes. in vitro, Biochem. Biophys. Res. Commun. 1974; 60: 1036
  • Mitchell J. R., Potter W. Z., Hinson J. A., Jollow D. J. Hepatic necrosis is caused by furosemide. Nature (London) 1974; 251: 508
  • Mitchell J. R., Nelson S. D., Potter W. Z., Sasame H. A., Jollow D. J. Metabolic activation of furosemide to a chemically reactive, hepatotoxic metabolite. J. Pharmacol. Exp. Ther. 1976; 41: 199
  • McMurtry R. J., Mitchell J. R. Renal and hepatic necrosis after metabolic activation of 2-substituted furans and thiophenes, including furosemide and cephaloridine. Toxicol. Appl. Pharmacol. 1977; 42: 285
  • Wirth P. J., Bettis C. J., Nelson W. L. Microsomal metabolism of furosemide. Evidence for the nature of the reactive intermediate involved in covalent binding. Mol. Pharmacol. 1976; 12: 759
  • Gurtoo H. L., Bejba N. Hepatic microsomal mixed-function oxygenase: enzyme multiplicity for the metabolism of carcinogens to DNA-binding metabolites. Biochem. Biophys. Res. Commun. 1974; 61: 735
  • Longo N., Boyd M. In vitro metabolic activation of the pulmonary toxin 4-ipomeanol, by lung slices and isolated whole lungs. Toxicol. Appl. Pharmacol. 1979; 48: A130
  • Saunders R., Griffith J., Saalfeld F. Identification of some organic smog components based on rain water analysis. Biomed. Mass Spectrom. 1974; 1: 192
  • Went F. W. Organic matter in the atmosphere, and its possible relation to petroleum formation. Proc. Natl. Acad. Sci. U.S.A. 1960; 46: 212
  • Rasmussen R. J. What do the hydrocarbons from trees contribute to air pollution. J. Air Pollut. Control Assoc. 1972; 22: 537
  • Smith G. Smog-origin-it may not be man-made. Rocky Mount. Med. J. 1967; 64: 55
  • Mathews J. Navy scientists' study hints trees to blame for D.C. pollution. The Washington Post June 10, 1975; Cl
  • Boyd M., Statham C, Franklin R., Mitchell J. Pulmonary bronchiolar alkylation and necrosis by 3-methylfuran, a naturally occurring potential atmospheric contaminant. Nature (London) 1978; 272: 270
  • Statham C. N., Franklin R. B., Boyd M. R. Pulmonary bronchiolar alkylation and necrosis by 3-methylfuran, a potential atmospheric contaminant derived from natural sources. Toxicol. Appl. Pharmacol. 1978; 45: 111
  • Statham C, Gilly P., Boyd M. unpublished results
  • Seawright A. A., Mattocks A. R. The toxicity of two synthetic 3-substituted furan carbamates. Experientia 1973; 29: 1197
  • Guengerich F. P. Studies on the activation of a model furan compound — toxicity and covalent binding of 2-(N-ethylcarbamoylhydroxymethyl) furan. Biochem. Pharmacol. 1909; 26, 1977
  • Wilson B. J., Garst J. E., Linnabary R. D., Channell R. B. Perilla ketone: a potent lung toxin from the mint plant,Perilla frutescens Britton. Science 1977; 197: 573
  • Franklin R. B., Boyd M. R. Studies on toxic, alkylating metabolites of 2-methylfuran. Toxicol. Appl. Pharmacol. 1978; 45: 279
  • Recknagel R. O. Carbon tetrachloride hepatotoxicity. Pharmacol. Rev. 1967; 19: 145
  • Villarruel M. C., Toranzo E. G., Castro J. A. Carbon tetrachloride activation, lipid peroxi-dation, and the mixed function oxygenase activity of various rat tissues. Toxicol. Appl. Pharmacol. 1977; 41: 337
  • Valdivia E., Sonnad J. Fatty change of the granular pneumocyte in CCI4 intoxication. Arch. Pathol. 1966; 81: 514
  • Gould V. E., Smuckler E. A. Alveolar injury in acute carbon tetrachloride intoxication. Arch. Intern. Med. 1971; 128: 109
  • Chen W. J., Chi E. Y., Smuckler E. A. Carbon tetrachloride-induced changes in mixed function oxidases and microsomal cytochromes in the rat lung. Lab. Invest. 1977; 36: 388
  • Longo N., Statham C, Sasame H., Boyd M. Pulmonary Clara-cell damage by carbon tetrachloride. Fed. Proc. 1978; 37: 505
  • Boyd M., Statham C, Longo N. The pulmonary clara cell as a target for toxic chemicals requiring metabolic activation; studies with carbon tetrachloride. J. Pharmacol. Exp. Ther. 1980; 212: 109
  • Willis R. J., Recknagel R. O. Potentiation by carbon tetrachloride of NADPH-dependent lipid peroxidation in lung microsomes. Toxicol. Appl. Pharmacol. 1979; 47: 89
  • Brodie B. B., Reid W. D., Cho A. K., Sipes G., Krishna G., Gillette J. R. Possible mechanism of liver necrosis caused by aromatic organic compounds. Proc. Natl. Acad. Sci. U.S.A. 1971; 68: 160
  • Reid W. D., Illett K. F., Glick J. M., Krishna G. Metabolism and binding of aromatic hydrocarbons in the lung. Am. Rev. Respir. Dis. 1973; 107: 539
  • Mahvi D., Bank H., Harley R. Morphology of a naphthalene-induced bronchiolar lesion. Am. J. Pathol. 1977; 86: 559
  • Jerina D. M., Daly J. W. Arene oxides: a new aspect of drug metabolism. Science 1974; 185: 573
  • Mackenzie J. B., Mackenzie C. G. Production of pulmonary edema by thiourea in the rat and its relation to age. Proc. Soc. Exp. Biol. Med. 1943; 54: 34
  • Dieke S. H., Richter C. P. Acute toxicity of thiourea to rats in relation to age, diet, strain and species variation. J. Pharmacol. Exp. Ther. 1945; 83: 195
  • Dieke S. H., Allen G. S., Richter C. P. The acute toxicity of thioureas and related compounds to wild and domestic Norway rats. J. Pharmacol. Exp. Ther. 1947; 90: 260
  • Richter C. P. The development and use of alphanaphthylthiourea (ANTU) as a rat poison. JAMA 1945; 129: 927
  • McClosky W. T., Smith M. I. Studies on the pharmacologic action and the pathology of alphanaphthylthiourea (ANTU). I. Pharmacology. Public Health Rep. 1945; 60: 1101
  • Dieke S. H., Richter C. P. Age and species variation in the acute toxicity of alphanaphthylthiourea. Proc. Soc. Exp. Biol. Med. 1946; 62: 22
  • Richter C. P. The physiology and cytology of pulmonary edema and pleural effusion produced in rats by alphanaphthylthiourea (ANTU). J. Thoracic Surg. 1952; 23: 66
  • Bohm G. M. Vascular permeability changes during experimentally produced pulmonary edema in rats. J. Pathol. Bacteriol. 1966; 92: 151
  • Cunningham A. L., Hurley J. V. Alphanaphthylthiourea-induced pulmonary edema in the rat: a topographical and electronmicroscope study. J. Pathol. 1972; 106: 25
  • Meyrick B., Miller J., Reid L. Pulmonary oedema induced by ANTU, or by high or low oxygen concentrations in rat — an electron microscope study. Br. J. Exp. Pathol. 1972; 53: 347
  • Saunders J. P., Spaulding R. C. Effects of some substituted thioureas on alphanaphthylthiourea (ANTU) toxicity to rats. Proc. Soc. Exp. Biol. Med. 1951; 76: 84
  • Byerrum R. U. Influence of dietary iodine on susceptibility of rats to alphanaphthylthiourea poisoning. Proc. Soc. Exp. Biol. Med. 1946; 62: 328
  • Van Den Brink H. A. S., Kelly H., Stone M. G. Innate and drug-induced resistance to acute lung damage caused in rats by α-naphthylthiourea (ANTU) and related compounds. Br. J. Exp. Pathol. 1976; 57: 621
  • Byerrum R. U., Dubois K. P. The influence of diet on the susceptibility of rats to alphanaphthylthiourea. J. Pharmacol. Exp. Ther. 1947; 90: 321
  • Byerrum R. U., Cochran K. W., Dubois K. P. Influence of alphanaphthylthiourea (ANTU) on iodine metabolism. Proc. Soc. Exp. Biol. Med. 1950; 73: 661
  • Richter C. P. Biological factors involved in poisoning rats with alphanaphthylthiourea. Proc. Soc. Exp. Biol. Med. 1946; 63: 364
  • Meyer B. J., Saunder J. P. The effects of thioureas and related compounds on alphanaphthylthiourea (ANTU) toxicity to rats. J. Pharmacol. Exp. Ther. 1949; 97: 432
  • Sobonya R. E., Kleinerman J. Recurrent pulmonary edema induced by α-naphthylthiourea. Am. Rev. Respir. Dis. 1973; 108: 926
  • Dubois K. P., Holm L. W., Doyle W. L. Biochemical changes following poisoning of rats by alphanaphthylthiourea. Proc. Soc. Exp. Biol. Med. 1946; 61: 102
  • Giri S. N., Combs A. B. Sulfur-containing compounds and tolerance in the prevention of certain metabolic effects of phenylthiourea. Toxicol. Appl. Pharmacol. 1970; 16: 709
  • Karel L., Meyer B. J. The effect of various sulfur-containing compounds on alphanaphthylthi-ourea (ANTU) toxicity to rats. J. Pharmacol. Exp. Ther. 1948; 93: 414
  • Giri S. N., Hollinger M. A., Cross C. E., Dungworth D. L. Effects of thiourea on pulmonary edema, pleural and peritoneal effusions and toxicity in rats pretreated with actinomycin. D, Toxicology 1974; 2: 211
  • Williams R. T. Acquisitions recentes dans l'etude du metabolism de substances toxiques. Ann. Biol. Clin. (Paris) 1965; 23: 7
  • Boyd M. R., Norman B. J., Neal R. A. Studies of toxicity and of development of tolerance of alphanaphthylthiourea (ANTU). Pharmacologist 1974; 16: 239
  • Hollinger M. A., Giri S. N., Alley M., Budd E., Hwang F. Tissue distribution and binding of radioactivity from14C-thiourea in the rat. Drug Metab. Dispos. 1974; 2: 521
  • Boyd M. R., Neal R. A. Studies on the mechanism of toxicity and of development of tolerance to the pulmonary toxin, α-naphthylthiourea (ANTU). Drug. Metab. Dispos. 1976; 4: 314
  • Hollinger M. A., Giri S. N., Hwang F. Binding of radioactivity from14C-thiourea to rat lung protein. DrugMetab. Dispos. 1976; 4: 119
  • Hollinger M. A., Giri S. N., Budd E. A pharmacodynamic study of [14C]-thiourea toxicity in immature, tolerant, and nontolerant rats. Toxicol. Appl. Pharmacol. 1976; 37: 545
  • Dalvi R. R., Poore R. E., Neal R. A. Studies of the metabolism of carbon disulfide by rat liver microsomes. Life Sci. 1974; 14: 1785
  • Kamataki T., Lee Lin M. C. M., Belcher D. H., Neal R. A. Studies of the metabolism of parathion with an apparently homogenous preparation of rabbit liver cytochrome P-450. Drug Metab. Dispos. 1976; 4: 180
  • Hunter A. L., Neal R. A. Inhibition of hepatic mixed-function oxidase activityin vitro andin vivo by various thiono-sulfur-containing compounds. Biochem. Pharmacol. 2199; 24, 1975
  • De Matteis F. Covalent binding of sulfur to microsomes and loss of cytochrome P-450 during the oxidative desulfuration of several chemicals. Mol. Pharmacol. 1974; 10: 849
  • De Matteis F., Seawright A. A. Oxidative metabolism of carbon disulfide by the rat. Effect of treatments which modify the liver toxicity of carbon disulfide. Chem. Biol. Interact. 1973; 7: 375
  • Bond E. J., De Matteis F. Biochemical changes in rat liver after administration of carbon disulfide, with particular reference to microsomal changes. Biochem. Pharmacol. 1969; 18: 2531
  • Poulsen L. L., Hyslop R. M., Ziegler D. M. S-oxidation of thioureylenes catalyzed by a microsomal flavoprotein mixed-function oxidase. Biochem. Pharmacol. 1974; 23: 3431
  • McLean E. K. The toxic actions of pyrrolizidine (Senecio) alkaloids. Pharmacol. Rev. 1970; 22: 429
  • Mattocks A. R. Toxicity and metabolism of Senecio alkaloids. Phytochemical Ecology, J. B. Har-borne. Academic Press, New York 1972, chap. 11
  • Mattocks A. R. Mechanisms of pyrrolizidine alkaloid toxicity. Proc. 5th Int. Congr. Pharmacology. S. Karger, Basel 1973; Vol. 2: 114
  • Jago M. V., Edgar J. A., Smith L. W., Culvenor C. C. J. Metabolic conversion of heliotri-dine-based pyrrolizidine alkaloids to dehydroheliotridine. Mol. Pharmacol. 1970; 6: 402
  • Hsu I. C., Allen J. R., Chesney C. F. Identification and toxicological effects of dehydroretro-necine, a metabolite of monocrotaline. Proc. Soc. Exp. Biol. Med. 1973; 144: 834
  • Mattocks A. R., White I. N. H. The conversion of pyrrolizidine alkaloids to N-oxides and to dihydropyrrolizine derivatives by rat liver microsomes. in vitro, Chem. Biol. Interact. 1971; 3: 383
  • Allen J. R., Carstens L. A. Pulmonary vascular occulusions initiated by endothelial lysis in monocrotaline-intoxicated rats. Exp. Mol. Pathol. 1970; 13: 159
  • Kay J. M., Heath D., Smith P., Bras G., Summerell J. Fulvine and the pulmonary circulation. Thorax 1971; 26: 249
  • Chesney C. F., Allen J. R. Monocrotaline induced pulmonary vascular lesions in non-human primates. Cardiovasc. Res. 1973; 7: 508
  • Wagenvoort C. A., Wagenvoort N., Dijk H. J. Effect of fulvine on pulmonary arteries and veins of the rat. Thorax 1974; 29: 522
  • Kay J. M., Smith P., Health D., Will J. A. Effects of phenobarbitone, cinnarizine, and zoxazolamine on the development of right ventricular hypertrophy and hypertensive pulmonary vascular disease in rats treated with monocrotaline. Cardiovasc. Res. 1976; 10: 200
  • Culvenor C. C. J., Edgar J. A., Jago M. V., Outteridge A., Peterson J. E., Smith L. W. Hepato- and pneumotoxicity of pyrrolizidine alkaloids in relation to molecular structure. Chem. Biol. Interact 1976; 12: 299
  • Butler W. H., Mattocks A. R., Barnes J. M. Lesions in the liver and lungs of rats given pyrrole derivatives of pyrrolizidine alkaloids. J. Pathol. 1970; 100: 169
  • Butler W. H. An ultrastructural study of the pulmonary lesion induced by pyrrole derivatives of the pyrrolizidine alkaloids. J. Pathol. 1970; 102: 15
  • Plestina R., Stoner H. B. Pulmonary oedema in rats given monocrotaline pyrrole. J. Pathol. 1972; 106: 245
  • Hurley J. V., Jago M. V. Pulmonary oedema in rats given dehydromonocrotaline: a topographic and electron-microscope study. J. Pathol. 1975; 117: 23
  • Plestina R., Stoner H. B., Jones G., Butler W. H., Mattocks A. R. Vascular changes in the lungs of rats after intravenous injection of pyrrole carbamates. J. Pathol. 1977; 121: 9
  • Chesney C. F., Allen J. R., Hsu I. C. Right ventricular hypertrophy in monocrotaline treated rats. Exp. Mol. Pathol. 1974; 20: 257
  • Allen J. R., Chesney C. F., Frazee W. J. Modifications of pyrrolizidine alkaloid intoxication resulting from altered hepatic microsomal enzymes. Toxicol. Appl. Pharmacol. 1972; 23: 470
  • Chesney C. F., Hsu I. C., Allen J. R. Modifications of thein vitro metabolism of the hepa-totoxic pyrrolizidine alkaloid, monocrotaline. Res. Commun. Chem. Pathol. Pharmacol. 1974; 8: 567
  • Huxtable R., Ciaramitaro D., Einstein D. The effect of a pyrrolizidine alkaloid, monocrotaline, and a pyrrole, dehydroretronecine, on the biochemical functions of the pulmonary endothelium. Mol. Pharmacol. 1978; 14: 1189
  • Smith P., Health D. Paraquat. CRC Crit. Rev. Toxicol. 1976; 4: 411
  • Biochemical Mechanisms of Paraquat Toxicity, A. P. Autor. Academic Press, New York 1977
  • Pasi A. The Toxicology of Paraquat, Diquat, and Morphamquat. Hans Huber, Bern 1978
  • Heath D., Smith P. The pathology of the lung in paraquat poisoning. Biochemical Mechanisms of Paraquat Toxicity, A. P. Autor. Academic Press, New York 1977; 39
  • Conning D. M., Fletcher K., Swan A. A. B. Paraquat and realted bipyridyls. Br. Med. Bull. 1969; 25: 245
  • Sharp C. W., Ottolenghi A., Posner H. S. Correlation of paraquat toxocity with tissue concentrations and weight loss in the rat. Toxicol. Appl. Pharmacol. 1972; 22: 241
  • Litchfield M. H., Daniel J. W., Longshaw S. The tissue distribution of the bipyridylium herbicides diquat and paraquat in rats and mice. Toxicology 1973; 1: 155
  • Murray R. E., Gibson J. E. Paraquat disposition in rats, guinea pigs and monkeys. Toxicol. Appl. Pharmacol. 1974; 27: 283
  • Ilett K. F., Stripp B., Menard R. H., Reid W. D., Gillette J. R. 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. 1974; 28: 216
  • Bus J. S., Preache M. M., Cagen S. Z., Poseur H. S., Eliason B. C., Sharp C. W., Gibson J. E. Fetal toxicity and distribution of paraquat and diquat in mice and rats. Toxicol. Appl. Pharmacol. 1975; 33: 450
  • Molnar I., Hayes W. Distribution and metabolism of paraquat in the rat. Toxicol. Appl. Pharmacol. 1971; 19: 405
  • Rose M. A., Smith L. L. Tissue uptake of paraquat and diquat. Gen. Pharmacol. 1977; 8: 173
  • Witschi H., Kacew S., Hirai K., Côté M. In vivo oxidation of reduced nicotinamide-adenine dinucleotide phosphate by paraquat and diquat in rat lung. Chem. Biol. Interact 1977; 19: 143
  • Rose M. S., Smith L. L., Wyatt I. Evidence for the energy dependent accumulation of paraquat into the lung. Nature (London) 1974; 252: 314
  • Rose M. S., Lock E. A., Smith L. L., Wyatt I. Paraquat accumulation. Tissue and species specificity. Biochem. Pharmacol. 1976; 25: 419
  • Rose M. S., Smith L. L. The relevance of paraquat accumulation by tissues. Biochemical Mechanisms of Paraquat Toxicity, A. P. Autor. Academic Press, New York 1977; 71
  • Lock E. A., Smith L. L., Rose M. S. Inhibition of paraquat accumulation in rat lung slices by a component of rat plasma and a variety of drugs and endogenous amines. Biochem. Pharmacol. 1976; 25: 1769
  • Smith L. L., Lock E. A., Rose M. S. The relationship between 5-hydroxytryptamine and paraquat accumulation into rat lung. Biochem. Pharmacol. 1976; 25: 2485
  • Sykes B. I., Purchase I. F. H., Smith L. L. Pulmonary ultrastructure after oral and intravenous dosage of paraquat to rats. J. Pathol. 1977; 121: 233
  • Daniel J. W., Gage J. C. Absorption and excretion of diquat and paraquat in rats. Br. J. lnd. Med. 1966; 23: 133
  • Hollinger M. A., Giri S. N. Binding of radioactivity from [14C] paraquat to rat lung protein. in vitro. Res. Commun. Chem. Pathol. Pharmacol. 1978; 19: 329
  • Bus J. S., Cagen S. Z., Olgaard M., Gibson J. E. A mechanism of paraquat toxicity in mice and rats. Toxicol. Appl. Pharmacol. 1976; 35: 501
  • Gage J. C. The action of paraquat and diquat on the respiration of liver cell fractions. Biochem. J. 1968; 109: 757
  • Bus J. S., Aust S. D., Gibson J. E. Superoxide- and singlet oxygen-catalyzed lipid peroxidation as a possible mechanism for paraquat (methyl viologen) toxicity. Biochem. Biophys. Res. Commun. 1974; 58: 749
  • Bassett D. J. P., Fisher A. B. Alterations of glucose metabolism during perfusion of rat lung with paraquat. Am. J. Physiol. 1978; 234: E653
  • Baldwin R. C., Pasi A., MacGregor J. T., Hine C. H. The rates of radical formation from the dipyridylium herbicides paraquat, diquat, and morfamquat in homogenates of rat lung, kidney, and liver: an inhibitory effect of carbon monoxide. Toxicol. Appl. Pharmacol. 1975; 32: 298
  • Farrington J. A., Ebert M., Land E. J., Fletcher K. Bipyridylium quaternary salts and related compounds. V. Pulse radiolysis studies of the reaction of paraquat radical with oxygen. Implications for the mode of action of bipyridyl herbicides. Biochim. Biophys. Acta. 1973; 314: 372
  • Davies D. S., Davies D. L. Effect ofd-propranolol and superoxide dismutase on paraquat reduction and adrenochrome formation by rat liver microsomes. Fed. Proc. 1974; 33: 228
  • Montgomery M. M. Interaction of paraquat with the pulmonary microsomal fatty acid desaturase system. Toxicol. Appl. Pharmacol. 1976; 36: 543
  • Mason R. P., Holtzman J. L. The role of catalytic superoxide formation in the O2 inhibition of nitroreductase. Biochem. Biophys. Res. Commun. 1975; 67: 1267
  • Fisher H. K., Clements J. A., Wright R. R. Enhancement of oxygen toxicity by the herbicide paraquat. Am. Rev. Respir. Dis. 1973; 107: 246
  • Bus J. S., Gibson J. E. Postnatal toxicity of chronically administered paraquat in mice and interactions with oxygen and bromobenzene. Toxicol. Appl. Pharmacol. 1975; 33: 461
  • Rhodes M. L., Zavala D. C., Brown D. Hypoxic protection in paraquat poisoning. Lab. Invest. 1976; 35: 496
  • Smith L. L., Rose M. S. Biochemical changes in lungs exposed to paraquat. Biochemical Mechanisms of Paraquat Toxicity, A. P. Autor. Academic Press, New York 1977; 187
  • Clark J. M., Lambertson C. J. Pulmonary oxygen toxicity: a review. Pharmacol. Rev. 1971; 23: 37
  • Crapo J. D., Tierney D. F. Superoxide dismutase and pulmonary oxygen toxicity. Am. J. Physiol. 1974; 226: 1401
  • Autor A. P. Reduction of parquat toxicity by superoxide dismutase. Life Sci. 1974; 14: 1309
  • Pederson T. C., Aust S. D. The role of superoxide and singlet oxygen in lipid peroxidation promoted by xanthineoxidase. Biochem. Biophys. Res. Commun. 1973; 52: 1071
  • Bus J. S., Aust S. D., Gibson J. E. Lipid peroxidation: a possible mechanism for paraquat toxicity. Res. Commun. Chem. Pathol. Pharmacol. 1975; 11: 31
  • Bus J. S., Aust S. D., Gibson J. E. Paraquat toxicity: proposed mechanism of action involving lipid peroxidation. Environ. Health Perspect 1976; 16: 139
  • Bus J. S., Aust S. D., Gibson J. E. Lipid peroxidation as a proposed mechanism for paraquat toxicity. Biochemical Mechanisms of Paraquat Toxicity, A. P. Autor. Academic Press, New York 1977; 157
  • Dodge A. D., Harris N. The mode of action of paraquat and diquat. Biochem. J. 1970; 118: 43P
  • Dodge A. D. The mode of action of the bipyridylium herbicides, paraquat and diquat. Endeavour 1971; 30: 130
  • King M. M., Lai E. K., McCay P. B. Singlet oxygen production associated with enzyme-catalyzed lipid peroxidation in liver microsomes. J. Biol. Chem. 1975; 250: 6496
  • Svingen B. A., O'Neal F. O., Aust S. D. The role of superoxide and singlet oxygen in lipid peroxidation. Photochem. Photobiol. 1978; 28: 803
  • Rotruck J. T., Pope A. L., Ganther H. E., Swanson A. B., Hafeman D. G., Hoekstra W. G. Selenium: biochemical role as a component of glutathione peroxidase. Science 1973; 179: 588
  • Christopherson B. O. Reduction of linolenic acid hydroperoxide by a glutathione peroxidase. Biochim. Biophys. Acta 1969; 176: 463
  • Omaye S. T., Reddy K. A., Cross C. E. Enhanced lung toxicity of paraquat in selenium-deficient rats. Toxicol. Appl. Pharmacol. 1978; 43: 237
  • Talcott R. E., Shu H., Wei E. T. Dissociation of microsomal oxygen reduction and lipid peroxidation with the electron acceptors, paraquat and menadione. Biochem. Pharmacol. 1979; 28: 665
  • Shu H., Talcott R. E., Rice S. A., Wei E. T. Lipid peroxidation and paraquat toxicity. Biochem. Pharmacol. 1979; 28: 327
  • Steffen C., Netter K. J. On the mechanism of paraquat action on microsomal oxygen reduction and its relation to lipid peroxidation. Toxicol. Appl. Pharmacol. 1979; 47: 593
  • Manktelow B. W. The loss of pulmonary surfactant in paraquat poisoning: a model for the study of the respiratory distress syndrome. Br. J. Exp. Pathol. 1967; 48: 366
  • Robertson B., Enhörning G., Ivemark B., Modée J. Experimental respiratory distress induced by paraquat. J. Pathol. 1971; 103: 239
  • Fisher H. K., Clements J. A., Wright R. R. Pulmonary effects of the herbicide paraquat studied 3 days after injection in rats. J. Appl. Physiol. 1973; 35: 268
  • Fisher H. K., Clements J. A., Tierney D. F., Wright R. R. Pulmonary effects of paraquat in the first day after injection. Am. J. Physiol. 1975; 228: 1217
  • Fletcher K., Wyatt I. The composition of lung lipids after poisoning with paraquat. Br. J. Exp. Pathol. 1970; 51: 604
  • Fletcher K., Wyatt I. The action of paraquat on the incorporation of palmitic acid into dipal-mitoyl lecithin in mouse lungs. Br. J. Exp. Pathol. 1972; 53: 225
  • Davies P., Allsion A. C. The significance of the lysosomes in toxicology. CRC Crit. Rev. Toxicol. 1972; 1: 283
  • Calderbank A. The bipyridylium herbicides. Adv. Pest Control Res. 1968; 8: 127
  • Goldberg B., Stern A. The role of the superoxide anion as a toxic species in the erythrocyte. Arch. Biochem. Biophys. 1977; 178: 218
  • Simons R. S., Jackett P. S., Carrol M. E. W., Lowrie D. B. Superoxide independence of paraquat toxicity in. Escherichia coli, Toxicol. Appl. Pharmacol. 1976; 37: 271
  • Davies D. S., Simons R. S., Jackett P. S., Carrol M. E., Lowrie D. B. Superoxide independence of paraquat toxicity in. Escherichia coli, Toxicol. Appl. Pharmacol. 1976; 37: 271, personal communication
  • Hassan H. M., Fridovich I. Superoxide radical and the oxygen enhancement of the toxicity of paraquat in. Escherichia coli, J. Biol. Chem. 1978; 253: 8113
  • Goldstein B. D., Rozen M. G., Quintavalla J. C., Amoruso M. A. Decrease in mouse lung and liver glutathione peroxidase activity and potentiation of the lethal effects of ozone and paraquat by the superoxide dismutase inhibitor, diethyldithiocarbamate. Biochem. Pharmacol. 1979; 28: 27
  • Rose M. S., Smith L. L., Wyatt I. The relevance of pentose phosphate pathway stimulation in rat lung to the mechanism of paraquat toxicity. Biochem. Pharmacol. 1976; 25: 1763
  • Schmitt S. L., Van Orden L. S., Autor A. P. Effect of paraquat on alveolar macrophages and type II pneumocytes isolated from rat lungs. Fed. Proc. 1977; 36: 413
  • Autor A. P., Witschi H., Kacew S., Hirai K., Cote M. in vivo oxidation of reduced nicotinamide-adenine dinucleotide phosphate by paraquat and diquat in rat lung. Chem. Biol. Interact. 1977; 19: 143, personal communication
  • Rosenow E. C. Drug-induced hypersensitivity disease of the lung. Immunologic and Infectious Reactions in the Lung, C. H. Kirkpatrick, Reynolds. Marcel Dekker, New York 1976; 261
  • Boyd M. R., Sasame H., Mitchell J. R., Catignani G. Dose-dependent pulmonary toxicity by nitrofurantoin and modification by dietary fat, vitamin E, and oxygen. Fed. Proc. 1977; 36: 405
  • Boyd M. R., Sasame H. A., Mitchell J. R., Stiko A., Catignani G. L. Acute pulmonary injury in rats by nitrofurantoin and modification by vitamin E, dietary fat, and oyxgen. Am. Rev. Respir. Dis. 1979; 120: 93
  • Statham C. N., Sasame H. A., Longo N. S., Boyd M. R. Unpublished results
  • Peterson F. Personal communication
  • Boyd M. R., Osborne B. A. Studies on microsomal nitroreductase in lung and liver which catalyzes covalent binding of14C-nitrofurantoin to pulmonary and hepatic protein. Fed. Proc. 1975; 34: 756
  • Boyd M. R., Stiko A., Sasame H. A. Metabolic activation of nitrofurantoin: possible implications for carcinogenesis. Biochem. Pharmacol. 1979; 28: 601
  • Wang C. Y., Behrens B. C., Ichikawa M., Bryan G. T. Nitroreduction of 5-nitrofuran derivatives by rat liver xanthine oxidase and reduced nicotinamide adenine dinucleotide phosphate — cytochrome creductase. Biochem. Pharmacol. 1974; 23: 3395
  • Buege J. A., Aust S. D. Comparative studies of rat liver and lung NADPH-cytochromec reductase. Biochim. Biophys. Acta 1975; 385: 371
  • Battelli M. G., Corte E. D., Stirpe G. Xanthine oxidase type D (dehydrogenase) in the intestine and other organs of the rat. Biochem. J. 1972; 126: 747
  • Mason R. P., Peterson F. J., Calaghan J. T., Hotzman J. L. Ascorbic acid destruction of the -O2 generated by nitrofurantoin and paraquat free radicals. Pharmacologist 1977; 19: 192
  • Sasame H. A., Boyd M. R. Superoxide and hydrogen peroxide production and NADPH oxidation stimulated by nitrofurantoin in lung microsomes: possible implications for toxicity. Life Sci. 1979; 24: 1091
  • Misra H. P., Fridovich I. The role of superoxide anion in the autooxidation of epinephrine and a simple assay for superoxide dismutase. J. Biol. Chem. 1972; 247: 3170
  • Aufrére M. B., Hoener B. A., Vore M. Reductive metabolism of nitrofurantoin in the rat. Drug Metab. Dispoc. 1978; 6: 403
  • Etherton J. E., Gresham G. A. Early bronchiolar damage following paraquat poisoning in mice. J. Pathol. 1979; 128: 21
  • Reznik-Schüller H., Lijinsky W. in vivo autoradiography and nitrosoheptamethyleine carcin-ogenesis in hamsters. Cancer Res. 1979; 39: 72
  • Grasso P., Williams M., Hodgson R., Wright M. G., Gangoli S. D. The histochemical distribution of aniline hydroxylase. Histochem. J. 1971; 3: 117
  • Harris C. C., Frank A. L., Van Haaften C, Kaufman D. G., Connor R., Jackson F., Barrett L. A., McDowell E. M., Trump B. F. Binding of3H-benzo(a)pyrene to DNA in cultured human bronchus. Cancer Res. 1976; 36: 1011
  • Yang S. K., Gelboin H. V., Trump B. F., Autrup H. and Harris, C. C, Metabolic activation of benzo(a)pyrene and binding to DNA in cultured human bronchus. Cancer Res. 1977; 37: 1210
  • Evans M. J., Johnson L. V., Stephens R. J., Freeman G. Renewal of the terminal bronchiolar epithelium in the rat following exposure to NO2 or O3. Lab. Invest. 1976; 35: 246
  • Evans M. J., Cabral-Anderson L. J., Freeman G. Role of the Clara cell in renewal of the bronchiolar epithelium. Lab. Invest. 1978; 38: 648
  • Lum H., Schwartz L. W., Dungworth D. L., Tyler W. S. A comparative study of cell renewal after exposure to ozone or oxygen. Response of terminal bronchiolar epithelium in the rat. Am. Rev. Respir. Dis. 1978; 118: 335
  • Tischler A. S. Small cell carcinoma of the lung: cellular origin and relationship to other neoplasms. Semin. Oncol. 1978; 5: 244
  • Wattenberg L. W., Leong J. L. Histochemical demonstration of reduced pyridine nucleotide dependent polycyclic hydrocarbon metabolizing systems. J. Histochem. Cytochem. 1962; 10: 412
  • Campiche M. A., Gautier A., Hernandez E. I., Reymond A. An electron microscopy study of the fetal development of human lung. Pediatrics 1963; 32: 976
  • Hage E. The morphological development of the pulmonary epithelium of human foetuses studied by light and electron microscopy. Z. Anat. Entwicklungsgesch 1973; 140: 271
  • O'Hare K. H., Sheridan M. N. Electron microscopic observations on the morphogenesis of the albino rat lung with special reference to pulmonary epithelial cells. Am. J. Anat. 1970; 127: 181
  • Huang T. W., Carlson J. R., Bray T. M., Bradley B. J. 3-Methylindole-induced pulmonary injury in goats. Am. J. Pathol. 1977; 87: 647
  • Adamson I. Y. R., Bowden D. H., Cote M. G., Witschi H. Lung injury induced by butylated hydroxytoluene-cytodynamic and biochemical studies in mice. Lab. Invest. 1977; 36: 26
  • Hirai K., Witschi H., Côté M. Electron microscopy of butylated hydroxytoluene-induced lung damage in mice. Exp. Mol. Pathol. 1977; 27: 295
  • Shaw Y. S., Chen C. Ring hydroxylation of di-t-butylhydroxytoluene by rat liver microsomal preparations. Biochem. J. 1972; 128: 1285
  • Nakagawa Y., Hiraga K., Suga T. Biological fate of butylated hydroxytoluene (BHT); bindingin vitro to liver microsomes. Chem. Pharm. Bull. 1979; 27: 480
  • Kehrer J., Witschi H. The role of metabolism in the pulmonary toxicity of butylated hydroxytoluene (BHT). Fed. Proc. 1979; 38: 582
  • Nakagawa Y., Hiraga K., Suga T. Biological fate of butylated hydroxytoluene (BHT); bindingin vivo of BHT to macromolecules of rat liver. Chem. Pharm. Bull. 1979; 27: 442
  • Williamson D., Esterez P., Witschi H. Studies on the pathogenesis of butylated hydroxytoluene-induced lung damage in mice. Toxicol. Appl. Pharmacol. 1978; 43: 577
  • Hook G. E. R., Bend J. R., Fouts J. R. Mixed-function oxidases and the alveolar macro-phage. Biochem. Pharmacol. 1972; 21: 3267
  • Harris C. C., Hsu I. C., Stoner G. D., Trump B. F., Selkirk J. K. Human pulmonary alveolar macrophages metabolise benzo(a)pyrene to proximate and ultimate mutagens. Nature (Lon-don) 1978; 272: 633
  • Witschi H. Proliferation of type II alveolar cells: a review of common responses in toxic lung injury. Toxicology 1976; 5: 267
  • Sebe Y. Perilla ketone. J. Chem. Soc. Jpn. 1943; 64: 1130
  • Brettner A., Heitman E. R., Woodin W. G. Pulmonary complications of drug therapy. Ra-diology 1970; 96: 31
  • Rosenow E. C. The spectrum of drug-induced pulmonary disease. Ann. Int. Med. 1972; 77: 977
  • Whitcomb M. E. Drug-induced lung disease. Chest 1973; 63: 418
  • Cole P. Drug-induced lung disease. Drugs 1977; 13: 422
  • Lippman M. Pulmonary reactions to drugs. Med. Clin. North Am. 1977; 61: 1353
  • Shanies H. M. Noncardiogenic pulmonary edema. Med. Clin. North Am. 1977; 61: 1319
  • Sostman H. D., Matthay R. A., Putman C. E. Cytotoxic drug-induced lung disease. Am. J. Med. 1977; 62: 608
  • Gould V. E., Miller J. Sclerosing alveolitis induced by cyclophosphamide. Am. J. Pathol. 1975; 81: 513
  • Olive P. L. Macromolecular, antineoplastic and radiosensitization effects of nitrofurans. Nitro-furans: Chemistry, Metabolism and Carcinogenesis, G. T. Bryan. Raven Press, New York 1978, chap. 5
  • Goodman J., Hochstein P. Generation of free radicals and lipid peroxidation by redox cycling of adriamycin and daunomycin. Biochem. Biophys. Res. Commun. 1977; 77: 797

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.