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

Nature. 1994 May 12;369(6476):154-6. doi: 10.1038/369154a0.


The metabolic activation or inactivation of carcinogens varies considerably in human populations, and is partly genetically determined. 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 exhaust. We have determined levels of DNA adducts in bladder cells and of 4-aminobiphenyl-haemoglobin 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetylation
  • Adult
  • Arylamine N-Acetyltransferase / genetics*
  • Arylamine N-Acetyltransferase / metabolism
  • Biotransformation
  • Caffeine / urine
  • Carcinogens, Environmental / metabolism*
  • Carcinogens, Environmental / pharmacokinetics
  • Cotinine / urine
  • DNA Damage
  • Genotype
  • Hemoglobins / analysis
  • Humans
  • Male
  • Middle Aged
  • Nicotine / urine
  • Phenotype
  • Polymorphism, Restriction Fragment Length
  • Smoking
  • Urinary Bladder / pathology


  • Carcinogens, Environmental
  • Hemoglobins
  • hemoglobin, 4-aminobiphenyl-
  • Caffeine
  • Nicotine
  • Arylamine N-Acetyltransferase
  • Cotinine