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Genetically based N-acetyltransferase metabolic polymorphism and low-level environmental exposure to carcinogens

Abstract

THE metabolic activation or inactivation of carcinogens varies considerably in human populations, and is partly genetically determined1,2. Inter-individual variability in the susceptibility to carcinogens may be particularly important at low degrees of environmental exposure. Examples of probable human carcinogens that present widespread low-dose exposures are environmental tobacco smoke and diesel exhaust3,4. We have determined levels of DNA adducts in bladder cells and of 4-aminobipheny7l–haemo-globin adducts in 97 volunteers, together with the N-acetylation non-inducible phenotype, the corresponding genotype, and the levels of nicotine–cotinine in the urine. We find that among the slow acetylators, 4-aminobiphenyl adducts were higher than in rapid acetylators at low or null nicotine–cotinine levels, whereas the difference between slow and rapid acetylators was less evident at increasing nicotine–cotinine levels. The N-acetyltransferase genotype is highly predictive of the acetylation phenotype. Our results indicate that the clearance of low-dose carcinogens is decreased in the genetically based slow-acetylator phenotype. Such genetic modulation of low-dose environmental risks is relevant to ‘risk assessment’ procedures.

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References

  1. Shields, P. G. & Harris, C. C. J. Am. med. Ass. 266, 681–687 (1991).

    Article  CAS  Google Scholar 

  2. Caporaso, N., Landi, M. T. & Vineis, P. Pharmacogenetics 1, 4–19 (1991).

    Article  CAS  Google Scholar 

  3. Woodward, A. & McMichael, A. J. Eur. J. Cancer 27, 1472–1478 (1991).

    Article  CAS  Google Scholar 

  4. IARC Monographs on The Evaluation of Carcinogenic Risks to Humans Vol. 46 (IARC, Lyon, 1989).

  5. Bartsch, H. et al. J. natn. Cancer Inst. 82, 1826–1831 (1990).

    Article  CAS  Google Scholar 

  6. Butler, M. A. et al. Pharmacogenetics 2, 116–127 (1992).

    Article  CAS  Google Scholar 

  7. Blum, M., Demierre, A., Grant, D. M., Heim, M. & Mayer, U. A. Proc. natn. Acad. Sci. U.S.A. 88, 5237–5241 (1991).

    Article  CAS  ADS  Google Scholar 

  8. Bell, D. M. et al. Carcinogenesis 14, 1689–1692 (1993).

    Article  CAS  Google Scholar 

  9. Bryant, M., Vineis, P., Skipper, P. & Tannenbaum, S. R. Proc. natn. Acad. Sci. U.S.A. 85, 9788–9791 (1988).

    Article  CAS  ADS  Google Scholar 

  10. Vineis, P. et al. Cancer Res. 50, 3002–3004 (1990).

    CAS  PubMed  Google Scholar 

  11. Talaska, G. et al. Cancer Epidem. 1, 61–66 (1991).

    CAS  Google Scholar 

  12. Talaska, G., Dooley, K. B. & Kadlubar, F. F. Carcinogenesis 11, 639–646 (1990).

    Article  CAS  Google Scholar 

  13. Talaska, G., Al-Juburi, A. Z. S. S. & Kadlubar, F. F. Proc. natn. Acad. Sci. U.S.A. 88, 5350–5454 (1991).

    Article  CAS  ADS  Google Scholar 

  14. Case, R. A. M. Ann. R. Coll. Surg. 39, 213–235 (1966).

    CAS  Google Scholar 

  15. IARC Monographs on The Evaluation of Carcinogenic Risks to Humans Vol. 4 (IARC, Lyon, 1974).

Download references

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Vineis, P., Bartsch, H., Caporaso, N. et al. Genetically based N-acetyltransferase metabolic polymorphism and low-level environmental exposure to carcinogens. Nature 369, 154–156 (1994). https://doi.org/10.1038/369154a0

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