Abstract
Genetic differences in the inducible arylhydrocarbon hydroxylase (EC 1.14.14.2) (AHH) system, which is involved in the multi-step metabolism of hydrocarbons, are known to exist in both humans and mice1–6. However, the predictive value of AHH activity in human or murine tissues, assayed as benzo(a)pyrene hydroxylation, as an index of individual susceptibility to mutagens and carcinogens, remains unclear5–8 because of apparent inconsistencies between results obtained from different in vitro and in vivo systems. This situation may in part reflect the complexity of the pathways involved in drug metabolism, which combine both activation and detoxification. To determine the relationship of metabolic potential to an easily quantified, short-term in vivo end point of genetic damage, we compared the ability of AHH inducible and uninducible mice to metabolize a procarcinogen, benzo(a)pyrene (BP), with the in vivo induction by BP of sister chromatid exchanges (SCEs). SCE induction has been shown to correlate with mutagensis9,10. We report here that although BP did cause an increase in SCEs in test animals, the extent of this increase did not differ between the inducible C57BL/6 mice and the uninducible DBA/2 mice. Moreover, prior exposure to an AHH inducer, 3-methylcholanthrene (3-MC), did not increase the number of BP-induced SCEs in C57BL/6 mice. This lack of correlation between benzo(a) pyrene hydroxylase (BP-OH) inducibility and SCE response reinforces the idea that other metabolic steps, such as detoxification or DNA repair, may influence the overall genetic impact of a drug.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 51 print issues and online access
$199.00 per year
only $3.90 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Nebert, D. W., Robinson, J. R., Niwa, A., Kumaki, K. & Poland, A. P. J. cell. Physiol. 85, 393–414 (1975).
Nebert, D. W., Atlas, S. A., Guenthner, T. M. & Kouri, R. E. in Polycyclic Hydrocarbons and Cancer Vol. 2 (eds Gelboin, H. & T'so, P.) 345–390 (Academic, New York, 1978).
Gelboin, H. V. & Blackburn, N. R. Cancer Res. 24, 356–360 (1964).
Wiebel, F. J., Leutz, J. C. & Gelboin, H. V. Archs Biochem. Biophys. 154, 292–294 (1973).
Kellermann, G., Shaw, C. R. & Luyten-Kellermann, M. New Engl. J. Med. 289, 934–937 (1973).
Paigen, B. H. et al. in Polycyclic Hydrocarbons and Cancer Vol. 2 (eds Gelboin, H. & T'so, P.) 391–408 (Academic, New York, 1978).
Kouri, R. E., Salerno, R. A. & Whitmire, C. E. J. natn. Cancer Inst. 50, 363–368 (1973).
Benedict, W. F., Considine, N. & Nebert, D. W. Molec. Pharmac. 6, 266–277 (1973).
Perry, P. & Evans, H. J. Nature 258, 121–125 (1975).
Carrano, A. V., Thompson, L. H., Lindl, P. A. & Minkler, J. L. Nature 271, 551–553 (1978).
Nebert, D. W. & Gelboin, H. V. J. biol. Chem. 243, 6242–6249 (1968).
Holder, G. et al. Proc. natn. Acad. Sci. U.S.A. 71, 4356–4360 (1974).
Schreck, R. R., Paika, I. J. & Latt, S. A. Mutat. Res. 64, 315–328 (1979).
Popescu, N. C., Turnbull, D. & DiPaolo, J. A. J. natn. Cancer Inst. 59, 289–293 (1977).
Nebert, D. W. J. natn. Cancer Inst. 64, 1279–1290 (1980).
Vogel, W. & Bauknecht, T. Nature 260, 448–449 (1976).
Thakker, D. R. et al. Proc. natn. Acad. Sci. U.S.A. 10, 3381–3385 (1976).
Rudiger, H. W. et al. Nature 262, 290–292 (1976).
Felton, J. S. & Nebert, D. W. J. biol. Chem. 250, 6769–6778 (1975).
Tucker, A. N. & Tang, T. J. envir. Path. Tox. 2, 613–623 (1979).
Phillips, D. H., Grover, P. L. & Sims, P. Int. J. Cancer 22, 487–494 (1978).
Bresnick, E. in In Vitro Metabolie Activation in Mutagenesis Testing (eds de Serres, F. J., Fouts, J. R., Bend, J. R. & Philpot, R. M.) 91–104 (Elsevier, Amsterdam, 1976).
Nebert, D. W., Thorgeirsson, S. S. & Felton, J. S. in In Vitro Metabolie Activation in Mutagenesis Testing (eds de Serres, F. J., Fouts, J. R., Bend, J. R. & Philpot, R. M.) 105–124 (Elsevier, Amsterdam, 1976).
Oesch, F. J. biol. Chem. 251, 79–87 (1976).
Hales, B. F. & Neims, A. H. Biochem. J. 160, 231–236 (1976).
Galloway, S. M., Perry, P. E., Meneses, J., Nebert, D. W. & Pedersen, R. A. Proc. natn. Acad. Sci. U.S.A. 77, 3524–3528 (1980).
Oesch, F., Jerina, D. M. & Daily, J. Biochim. biophys. Acta 227, 685–691 (1971).
Boobis, A. R., Reinhold, C. & Thorgiersson, S. Biochem. Pharmac. 26, 1501–1505 (1977).
Boobis, A. R., Nebert, D. W. & Felton, J. S. Molec. Pharmac. 13, 259–268 (1976).
Gielen, J. E., Goujon, F. M. & Nebert, D. W. J. biol. Chem. 247, 1125–1137 (1972).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Schreck, R., Latt, S. Comparison of benzo(a)pyrene metabolism and sister chromatid exchange induction in mice. Nature 288, 407–408 (1980). https://doi.org/10.1038/288407a0
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1038/288407a0
This article is cited by
-
In vitro induction of unscheduled DNA synthesis by genotoxic carcinogens in the hepatocytes of the oyster toadfish (Opsanus tau)
Archives of Environmental Contamination and Toxicology (1985)
Comments
By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.