Organ Specificity of Induction of Activating and Inactivating Enzymes by Cigarette Smoke and Cigarette Smoke Condensate

  • J. E. Gielen
  • F. Goujon
  • J. Sele
  • J. Van Cantfort
Part of the Archives of Toxicology book series (TOXICOLOGY, volume 2)

Abstract

Inhalation of cigarette smoke specifically induces the rat lung and kidney aryl hydrocarbon hydroxylase (AHH) in less than 4 h. The epoxide hydratase (EH) and the glutathione S-transferase are not significantly modified by a similar treatment in any of the rat tissues. Compared to the kidney AHH, the lung hydroxylase is 3–4 times more sensitive to small concentrations of cigarette smoke and seems to have a longer biological half-life. In both tissues, the induced AHH presents the same in vitro sensitivity to various inhibitors as a polycyclic hydrocarbon induced AHH.

In primary fetal rat liver cell culture, the cigarette smoke condensate fractions (CSCF) induce both the AHH and EH activity. Nevertheless, the AHH activity responds faster and to lower concentrations of CSCF than the EH activity. The liver cell culture constitutes a unique tool for a comparative study of the AHH and EH induction mechanism. Low concentration (10 µM) of benz(a)anthracene induces only the AHH activity while trans-stilbene oxide enhances selectively the EH activity. Appropriate concentrations of CSCF or of phenobarbital (PB) determine a parallel induction of both enzymes.

The results are discussed on the basis of (a) the existence of specific mechanisms of AHH regulation in the lung and in the kidney and (b) the existence of coordinated or independent biochemical control of the AHH and EH activity.

Key words

Monooxygenase Epoxide Hydratase Cigarette Smoke Induction Benzo(a)pyrene 

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References

  1. Abramson, R. K., Hutton, J. J.: Effects of cigarette smoking on aryl hydrocarbon hydroxylase activity in lungs and tissues of inbred mice. Cancer Res. 35, 23–29 (1975)PubMedGoogle Scholar
  2. Arias, I. M., Jacoby, W. B.: Glutathione — Metabolism and Function. New York: Raven Press 1976Google Scholar
  3. Atlas, S. A., Boobis, A. R., Felton, J. S., Thorgeirsson, S. S., Nebert, D. W.: Ontogenetic expression of polycyclic aromatic compound-inducible monooxygenase activities and forms of cytochrome P-450 in the rabbit. Evidence for temporal control and organ specificity of two genetic regulatory systems. J. Biol. Chem. 252, 4712–4721 (1977)PubMedGoogle Scholar
  4. Boyland, E., Chasseaud, L. F.: The role of glutathione S-transferases in mercapturic acid biosynthesis. Adv. Enzymol. 32, 172–219 (1969)Google Scholar
  5. Conney, A. H.: Pharmacological implications of microsomal enzyme induction. Pharmacol. Rev. 19, 317–366 (1967)PubMedGoogle Scholar
  6. Gielen, J. E., Heusghem, C., Nebert, D. W.: Mécanisme de l’induction de Phydroxylase des hydrocarbures aromatiques (AHH). In: Mises au point de Biochimie Pharmacologique, lère série. Siest, G., Heusghem, C. (eds.), p. 105–126. Paris: Masson 1977Google Scholar
  7. Gielen, J. E., Nebert, D. W.: Aryl hydrocarbon hydroxylase induction in mammalian cell culture. I. — Stimulation of enzyme activity in nonhepatic and hepatic cells by phenobarbital, polycyclic hydrocarbons and 2,2/-bis(p-chlorophenyl)-l,l,l-trichloroethane. J. Biol. Chem. 246, 5189–5198 (1971)PubMedGoogle Scholar
  8. Gielen, J. E., Nebert, D. W.: Aryl hydrocarbon hydroxylase induction in mammalian cell culture. III. — Effects of various sera, hormones, biogenic amines and other endogenous compounds on the enzyme activity. J. Biol. Chem. 247, 7591–7602 (1972)PubMedGoogle Scholar
  9. Heidelberger, C.: Chemical oncogenesis in culture. Adv. Cancer Res. 18, 317–366 (1973)PubMedCrossRefGoogle Scholar
  10. Heidelberger, C.: Chemical carcinogenesis. Ann. Rev. Biochem. 44, 79–121 (1975)PubMedCrossRefGoogle Scholar
  11. Jerina, D. M., Daly, J. W.: Arene oxides: A new aspect of drug metabolism. Science 185, 573–582 (1974)PubMedCrossRefGoogle Scholar
  12. Kouri, R. E., Rude, T., Thomas, P. E., Whitmire, C. E.: Studies on pulmonary aryl hydrocarbon hydroxylase activity in inbred strains of mice. Chem. Biol. Interact. 13, 317–331 (1976)PubMedCrossRefGoogle Scholar
  13. Lowry, O., Rosebrough, N., Farr, A., Randall, R.: Protein measurement with the folin phenol reagent. J. Biol. Chem. 193, 265–275 (1951)PubMedGoogle Scholar
  14. Miller, E. C., Miller, J. A.: The metabolism of chemical carcinogens to reactive electrophiles and their possible mechanism of action in carcinogenesis. In: Chemical carcinogens. Searle, C. E. (ed.), p. 737–762, ACS monograph 173. Washington D.C. 1976Google Scholar
  15. Montesano, R., Bartsch, H.: Mutagenic and carcinogenic N-nitroso compounds: possible environmental hazards. Mutat. Res. 32, 179–228 (1976)PubMedGoogle Scholar
  16. Montesano, R., Magee, P. N.: Comparative metabolism in vitro of nitrosamines in various animal species including man. In: Chemical carcinogenesis essays, IARC scientific publications n° 10. Montesano, R., Tomatis, L. (eds.), p. 39–56. Lyon: IARC 1974Google Scholar
  17. Nebert, D. W., Gielen, J. E.: Aryl hydrocarbon hydroxylase induction in mammalian cell culture. II. — Effects of actinomycin D and cycloheximide on induction processes by phenobarbital or polycyclic hydrocarbons. J. Biol. Chem. 246, 5199–5206 (1971)PubMedGoogle Scholar
  18. Nebert, D. W., Gielen, J. E.: Genetic regulation of aryl hydrocarbon hydroxylase induction in the mouse. Fed. Proc. 31, 1315–1325 (1972)PubMedGoogle Scholar
  19. Oesch, F.: Epoxide hydratase. In: Mises au point de Biochimie Pharmacologique, lère série. Siest, G., Heusghem, C. (eds.), p. 127–148. Paris: Masson 1977Google Scholar
  20. Oesch, F., Raphael, D., Schwind, H., Glatt, H. R.: Species differences in activating and inactivating enzymes related to the control of mutagenic metabolites. Arch. Toxicol. 39, 97–108 (1977)PubMedCrossRefGoogle Scholar
  21. Oesch, F., Schmassmann, H.: Species and organ specificity of the trans-stilbene oxide induced effects on epoxide hydratase and benz(a)pyrene monooxygenase activity in rodents. Biochem. Pharmacol. 28, 171–176 (1979)PubMedCrossRefGoogle Scholar
  22. Owens, I. S., Nebert, D. W.: Aryl hydrocarbon hydroxylase induction in mammalian-liver-derived cell cultures. Stimulation of “cytochrome P1-450 associated” enzyme activity by many inducing compounds. Mol. Pharmacol. 11, 94–104 (1975)PubMedGoogle Scholar
  23. Schmassmann, H. V., Glatt, H. R., Oesch, F.: A rapid assay for epoxide hydratase activity with benzo(a)pyrene 4,5-(K-region-)oxide as substrate. Anal. Biochem. 74, 94–104 (1976)PubMedCrossRefGoogle Scholar
  24. Schmassmann, H. V., Sparrow, A., Platt, K., Oesch, F.: Epoxide hydratase and benzo(a)pyrene monooxygenase activities in liver, lung and kidney after treatment of rats with epoxides of widely varying structures. Biochem. Pharmacol. 27, 2237–2245 (1978)PubMedCrossRefGoogle Scholar
  25. Sims, P., Grover, P. L.: Epoxides in polycyclic aromatic hydrocarbon metabolism and carcinogenesis. Adv. Cancer Res. 20, 165–274 (1974)PubMedCrossRefGoogle Scholar
  26. Sims, P., Grover, P. L., Swaisland, A., Pal, K., Hewer, A.: Metabolic activation of benzo(a)pyrene proceeds by a diol-epoxide. Nature 252, 326–328 (1974)PubMedCrossRefGoogle Scholar
  27. Swain, A. P., Cooper, J. E., Stedman, R. L.: Large-scale fractionation of cigarette smoke condensate for chemical and biological investigations. Cancer Res. 29, 579–583 (1969)PubMedGoogle Scholar
  28. Thorgeirsson, S. S., Nebert, D. W.: The Ah locus and the metabolism of chemical carcinogens and other foreign compounds. Adv. Cancer Res. 25, 149–193 (1977)PubMedCrossRefGoogle Scholar
  29. Van Cantfort, J., De Graeve, J., Gielen, J. E.: Radioactive assay for aryl hydrocarbon hydroxylase. Improved method and biological importance. Biochem. Biophys. Res. Commun. 79, 505–512 (1977)PubMedCrossRefGoogle Scholar
  30. Van Cantfort, J., Gielen, J. E.: Organ specificity of aryl hydrocarbon hydroxylase induction by cigarette smoke in rats and mice. Biochem. Pharmacol. 24, 1253–1256 (1975)PubMedCrossRefGoogle Scholar
  31. Van Cantfort, J., Gielen, J. E.: Induction by cigarette smoke of aryl hydrocarbon hydroxylase activity in the rat kidney and lung. Int. J. Cancer, 19, 538–545 (1977)PubMedCrossRefGoogle Scholar
  32. Van Cantfort, J., Manil, L., Gielen, J. E., Glatt, H. R., Oesch, F.: A new assay for glutathione S-transferase using [3H]-benzo(a)pyrene 4,5-oxide as substrate. Inducibility by various chemicals in different rat tissues compared to that of aryl hydrocarbon hydroxylase and epoxide hydratase. Biochem. Pharmacol. 28, 455–460 (1979)PubMedCrossRefGoogle Scholar
  33. Weisburger, E. K.: Mechanisms of chemical carcinogenesis. Ann. Rev. Pharmacol. Toxicol. 18, 395–416 (1978)CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 1979

Authors and Affiliations

  • J. E. Gielen
    • 1
  • F. Goujon
    • 1
  • J. Sele
    • 1
  • J. Van Cantfort
    • 1
  1. 1.Laboratoire de Chimie MédicaleInstitut de PathologieSart Tilman par Liège 1Belgium

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