title: Modulation of urinary mutagenicity by genetically determined carcinogen metabolism in smokers.
abstract: We examined the genotypes of two polymorphic genes involved in the detoxification of several mutagenic and carcinogenic compounds in relation to tobacco smoking-associated urinary mutagenicity. The genes studied were the glutathione S-transferase-encoding GSTM1 gene and acetyltransferase-encoding NAT2 gene. Smokers with no GSTM1 gene (n = 7) had urine that was several times more mutagenic than that of smokers with the gene (n = 10). The mean level of urinary mutagenicity in presence of metabolic activation was 2527 +/- 958 revertants/100 ml urine for GSTM1-smokers compared to 766 +/- 560 revertants/100 ml for GSTM1+ smokers (P < 0.001) using the bacterial strain YG1024. The corresponding values using the TA98 strain were 336 +/- 124 and 123 +/- 75 (P < 0.001). In contrast, we failed to show any difference in the level of urinary mutagenicity between slow-acetylator and fast-acetylator NAT2 genotypes among smokers (n = 17) or non-smokers (n = 35). Our results offer one explanation for the recent findings that GSTM1 polymorphism is a risk modifier in smoking-related cancers, especially bladder cancer.
authors.affiliation: Department of Industrial Hygiene and Toxicology, Institute of Occupational Health, Helsinki, Finland.
authors.forename: A
authors.initials: A
authors.lastname: Hirvonen
authors.forename: L
authors.initials: L
authors.lastname: Nylund
authors.forename: P
authors.initials: P
authors.lastname: Kociba
authors.forename: K
authors.initials: K
authors.lastname: Husgafvel-Pursiainen
authors.forename: H
authors.initials: H
authors.lastname: Vainio
mesh_terms: D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D001711:Biotransformation; D002273:Carcinogens / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009152:Mutagenicity Tests; D009153:Mutagens / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity*; D012907:Smoking / Q000235:genetics* / Q000652:urine*
chemical_list: D002273:Carcinogens; D009153:Mutagens; D001191:Arylamine N-Acetyltransferase; D005982:Glutathione Transferase