The Metabolism of Chemicals by the Lung

  • Gerald M. Cohen
Part of the Ettore Majorana International Science Series book series (EMISS, volume 6)


The lung, due to its position between ‘le milieu interieur’ and the outside environment, is exposed both to a wide variety of environmental chemicals including atmospheric pollutants and cigarette smoke and also to chemicals in the systemic circulation. Many of these chemicals may be metabolised in the lung possibly modifying their pharmacological, therapeutic or toxicological actions. Many xenobiotics (foreign chemicals) are metabolised by pulmonary microsomal mixed function oxidases, with very broad substrate specificities. The oxidation products of these pulmonary mixed function oxidase may be altered by a wide variety of environmental factors, in particular diet and cigarette smoke. Such variations in enzyme activities could lead to alterations of the pharmacology, toxicology or carcinogenicity of the xenobiotic. the localisation of high concentrations of cytochrome P-450 in the Clara cell may be the molecular basis for the organ specificity of several pulmonary toxins.


Reactive Metabolite Clara Cell Mixed Function Oxidase Aryl Hydrocarbon Hydroxylase Human Bronchus 
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  1. 1.
    G.M. Cohen, Pulmonary metabolism of inhaled chemicals and irritants, in Scientific Foundations of Respiratory Medicine, eds. J.G. Scadding and G. Cumming. W. Heinemann Ltd. In Press.Google Scholar
  2. 2.
    G.M. Cohen, Pulmonary metabolism of inhaled sustances and possible relationship with carcinogenicity and toxicity, in Lung Metabolism, eds. A.F. Junod and R. de Haller, Academic Press, New York, 1975.Google Scholar
  3. 3.
    G.E.R. Hook and J.R. Bend, Pulmonary metabolism of xenobiotics, Life Sci. 18:279 (1976).PubMedCrossRefGoogle Scholar
  4. 4.
    R.M. Philpot, M.W. Anderson and T.E. Eling, Uptake, accumulation and metabolism of chemicals by the lung, in Metabolic Functions of the Lung, eds. Y.S. Bakhle and J.R. Vane Marcel Dekker Inc. New York, 1977.Google Scholar
  5. 5.
    Y.S. Bakhle and J.R. Vane, Pharmocokinetic function of the pulmonary circulation, Physiol. Rev. 54:1007 (1974).PubMedGoogle Scholar
  6. 6.
    J.R. Fry and J.W. Bridges, in Progress in Drug Metabolism, Vol.2, eds. J.W. Bridges and L.F. Chasseaud, Wiley and Sons, London, 1977.Google Scholar
  7. 7.
    L.W. Wattenberg and J.L. Leong, Tissue distribution studies of polycyclic hydrocarbon hydroxylase activity, in Handbook of Experimental Pharmacology, Vol. 28/2, eds. B.B. Brodie and J. Gillette, Springer-Verlag, Berlin, 1971.Google Scholar
  8. 8.
    E.A.B. Brown, The localisation, metabolism and effects of drugs and toxicants in lung, Drug Metab. Rev., 3:33 (1974).PubMedCrossRefGoogle Scholar
  9. 9.
    R.T. Williams, The metabolism and detoxication of drugs, toxic substances and other organic compounds, Chapman and Hall Ltd., London, 1959.Google Scholar
  10. 10.
    T.E. Gram, Comparitive aspects of mixed function oxidation by lung and liver of rabbits, Drug Metab. Rev., 2:1 (1973).PubMedCrossRefGoogle Scholar
  11. 11.
    P. Simms, P.L. Grover, A. Swaisland, K. Pal and A. Hewer, Metabolic activation of benzo(a)pyrene proceeds by a diol-epoxide, Nature, 252:326 (1974).CrossRefGoogle Scholar
  12. 12.
    L.W. Wattenberg, Dietry modifications of intestinal and pulmonary aryl hydrocarbon hydroxylase activity, Tox. Appl. Pharmacol., 23:741 (1972).CrossRefGoogle Scholar
  13. 13.
    J.R. Fouts and T.R. Devereux, Developmental aspects of hepatic and extrahepatic drug-metabolizing enzyme systems: Microsomal enzymes and components in rabbit liver and lung during the first month of life, J. Pharmacol. Exp. Ther., 183:458 (1972).PubMedGoogle Scholar
  14. 14.
    C.R. Wolf, B.R. Smith, L.M. Ball, C. Serabjit-Singh, J.R. Bend and R.M. Philpot, 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 (1979).PubMedGoogle Scholar
  15. 15.
    E.C. Miller, Some current perspectives on chemical carcinogenesis in humans and experimental animals: Presidential address. Cancer Res., 38:1479 (1978).PubMedGoogle Scholar
  16. 16.
    M.R. Boyd, Evidence for the Clara cell as a site of cytochrome P-450-dependent mixed-function oxidase activity in lung, Nature, 269:713 (1977).PubMedCrossRefGoogle Scholar
  17. 17.
    M.R. Boyd and L.T. Burka, 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., 207:687 (1978).PubMedGoogle Scholar
  18. 18.
    C.J. Serab Jit-Singh, CR. Wolf, R.M. Philpot and C.G. Plopper, Cytochrome P-450: Localization in rabbit lung, Science, 207:1469 (1980).CrossRefGoogle Scholar
  19. 19.
    P. Grasso, M. Williams, R. Hodgson, M.G. Wright and S.D. Gangolli, The histochemical distribution of aniline hydroxylase in rat tissues, Histochem. J., 3:117 (1971).PubMedCrossRefGoogle Scholar
  20. 20.
    W.D. Reid, J.M. Glick and G. Krishna, Metabolism of foreign compounds by alveolar macrophages of rabbits, Biochem. Biophys. Res. Commun., 49:626 (1972).PubMedCrossRefGoogle Scholar
  21. 21.
    G.E.R. Hook, J.R. Bend and J.R. Fouts, Mixed function oxidases of the alveolar macrophage, Biochem. Pharmacol., 21:3267 (1972).PubMedCrossRefGoogle Scholar
  22. 22.
    C.C. Harris, I.C. Hsu, G.D. Stoner, B.F. Trump and J.K. Selkirk Human pulmonary alveolar macrophages metabolise benzo(a)pyrene to proximate and ultimate mutagens, Nature, 272:633 (1978).PubMedCrossRefGoogle Scholar
  23. 23.
    G.M. Cohen, S.M. Haws, B.P. Moore and J.W. Bridges, Benzo(a)pyren-3-yl hydrogen sulphate, a major ethyl acetate-extractable metabolite of benzo(a)pyrene in human, hamster and rat lung cultures, Biochem. Pharmacol., 25:2561 (1976).PubMedCrossRefGoogle Scholar
  24. 24.
    H. Autrup, F.C. Wefald, A.M. Jeffrey, H. Tate, R.D. Schwarz, B.F. Trump and C.C. Harris, Metabolism of benzo(a)pyrene by cultured tracheobronchial tissues from mice, rats, hamsters, bovines and humans, Int. J. Cancer, 25:293 (1980).PubMedCrossRefGoogle Scholar
  25. 25.
    C.C. Harris, H. Autrup, R. Connor, L.A. Barrett, E.M. McDowell and B.F. Trump, Inter individual variation in binding of benzo(a)pyrene to DNA in cultured human bronchi, Science, 194:1067 (1976).PubMedCrossRefGoogle Scholar
  26. 26.
    P.L. Grover, K. Pal, A. Hewer and P. Sims, The involvement of a diol-epoxide in the metabolic activation of benzo(a)pyrene in human bronchial mucosa and mouse skin. Int. J. Cancer, 18:1 (1976).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1982

Authors and Affiliations

  • Gerald M. Cohen
    • 1
  1. 1.Department of BiochemistyUniversity of SurreyGuildford, SurreyEngland

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