Urinary mutagenicity on TA98 and YG1024 Salmonella typhimurium strains after a hamburger meal: influence of GSTM1 and NAT2 genotypes.
Mutagenicity on TA98 and YG1024 Salmonella typhimurium strains of pan-fried hamburger extracts and of 24 h post-meal urine from 32 non-smoking volunteers was evaluated. Each participant in the study was GSTM1 and NAT2 genotyped. After cooking the meat showed mutagenic activity (mean +/- SD) on strains TA98 and YG1024 of 114 +/- 129 and 1437 +/- 1536 net revertants/g respectively. Twenty three of 32 urine samples showed clear mutagenic activity (i.e. caused at least a doubling of the number of spontaneous revertants) on the O-acetyltransferase over-producing strain YG1024, while none of the post-meal 24 h urine samples was clearly mutagenic on strain TA98. Total 24 h post-meal YG1024-active urinary mutagens were well correlated with the levels of mutagen intake with the meal (r2 = 0.5977, F = 44.58, P < 0.01). In the group under study GSTM1 genotypes did not influence urinary mutagenicity. Highly exposed subjects (n = 15) with the NAT2-ss genotype showed significantly increased levels of urinary mutagenicity on strain YG1024 in comparison with NAT2-R subjects (mutagen intake-adjusted total 24 h mutagen excretion = 1.00 +/- 0.29 versus 0.66 +/- 0.32, Mann-Whitney U test, U = 12.5, P < 0.05). Our results suggest that the levels of urinary mutagens derived from diets rich in heterocyclic aromatic amines, which are specifically detected by the YG1024 Salmonella strain, are modulated by NAT2-dependent enzyme activity, slow acetylators having higher levels of mutagens in their urine. Subjects with the rapid acetylator genotype, who are known to be at risk for colon cancer, seem to be partially protected with respect to the risk of bladder cancer.
Gabbani
G
G
Institute of Occupational Health, University of Padova, Italy.
Nardini
B
B
Bordin
A
A
Pavanello
S
S
Janni
L
L
Celotti
L
L
Clonfero
E
E
D000818:Animals; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D002417:Cattle; D003296:Cooking; D005260:Female; D005838:Genotype; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D008297:Male; D008460:Meat / Q000009:adverse effects*; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000008:administration & dosage* / Q000302:isolation & purification; D012486:Salmonella typhimurium / Q000201:enzymology* / Q000235:genetics*; D014556:Urine / Q000737:chemistry* / Q000382:microbiology
D009153:Mutagens; D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human; D005982:Glutathione Transferase