Abstract
Certain polycyclic aromatic hydrocarbons (PAHs) have been reported to induce cytochrome P450 (CYP) 1A1 and 1A2. In the present study, the effects of six well-known PAHs, such as benzo[a]pyrene, benz[a]anthracene, dibenz[a, h]anthracene, chrysene, benzo[k]fluorancene and benzo[b]fluorancene, on the activities of hepatic and pulmonary CYP enzymes were investigated in male ICR mice. When mice were treated intraperitoneally with 3, 10 and 30 mg/kg of individual PAHs for 3 consecutive days, the activities of ethoxyresorufin- and methoxyresorufin-O-dealkylases were significantly and differentially induced in both liver and lung. Moreover, other CYP isozyme-associated monooxygenase activities were also induced significantly in liver and lung with characteristic induction profiles. Our present results suggest that individual PAHs might have inductive effects on CYP isozymes, and that the characteristic inductive effects of individual PAHs on certain CYP isozymes would be developed as a marker for determining exposure to certain PAHs.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Blank, J. A., Tucker, A. N., Sweatlock, J., Gasiewicz, T. A., and Luster, M. I., α-Naphthoflavone antagonism of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin induced murine ethoxyresorufinO-deethylase activity and immunosuppression.Mol. Pharmacol., 32, 168–172 (1987).
Brunstrom, B., Broman, D., and Naf, C., Toxicity and EROD-inducing potency of 24 polycyclic aromatic hydrocarbons (PAHs) in chick embryos.Arch. Toxicol., 65, 485–489 (1991).
Buckly, T. J. and Lioy, P. J., An examination of the time course from human dietary exposure to polycyclic aromatic hydrocarbons to urinary elimination of 1-hydroxypyrene.Br. J. Ind. Med., 49, 113–124 (1992).
Conney, A. H., Induction of microsomal enzymes by foreign chemicals and carcinogenesis by polycyclic aromatic hydrocarbons: G. H. A. Clowes Memorial Lecture.Cancer Res., 42, 4875–4917 (1982).
Conney, A. H., Chang, R. L. Jerina, D. M., and Wei, S. J., Studies on the metabolism of benzo[a]pyrene and dose-dependent difference in the mutagenic profile of its ultimate carcinogenic metabolite.Drug Metab. Rev., 26, 125–163 (1994).
Dipple, A., Michejda, C. J., and Weisburger, E. M., Metabolism of chemical carcinogens.Pharmacol. Ther., 27, 265–296 (1985).
Gelboin, H. V., Benzo[a]pyrene metabolism, activation, and carcinogenesis: role and regulation of mixed function oxidases and related enzymes.Physiol. Rev., 60, 1107–1166 (1980).
Guengerich, F. P., Metabolism of chemical carcinogens.Carcinogenesis, 21, 345–351 (2000).
Guengerich, F. P., Human cytochrome P450 enzymes, in: PR. Ortiz de Mentellano (Ed.), Cytochrome P450, Plenum Press, New York, 473–535 (1995).
Guengerich, F. P. and Shimada, T., Activation of procarcinogens by human cytochrome P450 enzymes.Mutation Res., 400, 201–213 (1998).
Guengerich, F. P. and Shimada, T., Oxidation of toxic and carcinogenic chemicals by human cytochrome P-450 enzymes.Chem. Res. Toxicol., 4, 391–407 (1991).
Heidelberger, C., Chemical carcinogenesis.Annu. Rev. Biochem., 44, 79–121 (1975).
IARC, Polynuclear aromatic compounds,IARC Monographs on the Evaluation of the Carcinogenic Risks of Chemical to Humans, 32, 355-364, World Health Organization, Lyon, France (1983).
Kielhom, J. and Boehnicke, A., Guidelines for drinking water quality. Addendum to vol. 2 Health criteria and other supporting information, 2nd edition. World Health Organization, Geneva, 123–152 (1998).
Koop, D. R., Hydroxylation ofp-nitrophenol by rabbit ethanol-inducible cytochrome P450 isozyme 3a.Mol. Pharmacol., 29, 399–404 (1986).
Lowry, O. H., Rosebrough, N. H., Farr, A. L. and Randall, R. J., Protein measurement with folin phenol reagent.J. Biol. Chem., 193, 265–275 (1951).
Lubet, R. A., Meyer, R. T., Cameron, J. W., Nims, R. W., Burke, M. D., Wolff, J., and Guengerich, F. P., Dealkylation of pentoxyresorufin: a rapid and sensitive assay for measuring induction of cytochrome(s) P-450 by phenobarbital and other xenobiotics in the rat.Arch. Biochem. Biophys., 238, 43–48 (1985)
Machala, M., Matlova, L., Svoboda, I., and Nezveda, K., Induction effects of polychlorinated biphenyls, polycyclic aromatic hydrocarbons and other widespread aromatic environmental pollutants on microsomal monooxygenase activities in chick embryo liver.Arch. Toxicol., 70, 362–367 (1996).
Menzie, C. A., Potocki, B. B., and Santodonato, J., Exposure to carcinogenic PAHs in the environment.Environ. Sci. Technol., 26, 1278–1284 (1992).
Nash, T., The colorimetric estimation of formaldehyde by means of the Hantzsch reaction.Biochem. J., 55, 416–421 (1953).
Nisbet, I. C. T. and LaGoy, P. K., Toxic equivalency factors (TEFs) for polycyclic aromatic hydrocarbons (PAHs). Reg. 7ox/′co/.Pharmacol., 16, 290–300 (1992).
Petry, T., Schmid, P., and Schlatter, C., The use of toxic equivalency factors in assessing occupational and environmental health risk associated with exposure to airborne mixtures of polycyclic aromatic hydrocarbons (PAHs).Chemosphere, 32, 639–648 (1996).
United States Environmental Protection Agency (USEPA),Provisional Guidance for Quantitative Risk Assessment of Polycyclic Aromatic Hydrocarbons, EPA/600/R-93/089. United States Environmental Protenction Agency (1993).
Villeneuve, D. L., Crunkilton, R. L., and DeVita, W. M., Identification of cytochrome P4501A inducers in complex mixtures of polycyclic aromatic hydrocarbons (PAHs).Society of Environmental Toxicology and Chemistry, Second World Congress, Vancouver, Canada, Abstract No. PT215 (1995).
White, K. L., Jr., Lysy, H. H., and Holsapple, M. P., Immunosuppression by polycyclic aromatic hydrocarbons: a structure-activity relationship in B6C3F1 and DBA/2 mice.Immuno-pharmacology, 9, 155–164 (1985).
Willett, K. L., Gardinali, P. R., Sericano, J. L., Wade, T. L., and Safe, S. H., Characterization of the H4IIE rat hepatoma cell bioassay for evaluation of environmental samples containing polynuclear aromatic hydrocarbons (PAHs).Arch. Environ. Contam. Toxicol., 32, 442–448 (1997).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Kim, J.Y., Lee, S.K., Kim, C.H. et al. Effects of polycyclic aromatic hydrocarbons on liver and lung cytochrome P450s in Mice. Arch Pharm Res 26, 394–404 (2003). https://doi.org/10.1007/BF02976697
Received:
Issue Date:
DOI: https://doi.org/10.1007/BF02976697