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-smoki ng volunteers was evaluated. Each participant in the study was GSTM1 a nd NAT2 genotyped. After cooking the meat showed mutagenic activity (m ean +/- SD) on strains TA98 and YG1024 of 114 +/- 129 and 1437 +/- 153 6 net revertants/g respectively. Twenty three of 32 urine samples show ed clear mutagenic activity (i.e. caused at least a doubling of the nu mber of spontaneous revertants) on the O-acetyltransferase overproduci ng strain YG1024, while none of the post-meal 24 h urine samples was c learly mutagenic on strain TA98. Total 24 h post-meal YG1024-active ur inary mutagens were web correlated with the levels of mutagen intake w ith the meal (r(2) = 0.5977, F = 44.58, P < 0.01). In the group under study GSTM1 genotypes did not influence urinary mutagenicity, Highly e xposed subjects (n = 15) with the NAT2-ss genotype showed significantl y increased levels of urinary mutagenicity on strain YG1024 in compari son with NAT2-R subjects (mutagen intake-adjusted total 24 h mutagen e xcretion = 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 muta gens derived from diets rich in heterocyclic aromatic amines, which ar e specifically detected by the YG1024 Salmonella strain, are modulated by NAT2-dependent enzyme activity, slow acetylators having higher lev els of mutagens in their urine. Subjects with the rapid acetylator gen otype, who are known to be at risk for colon cancer, seem to be partia lly protected with respect to the risk of bladder cancer.