PILOT-STUDY OF FREE AND CONJUGATED URINARY MUTAGENICITY DURING CONSUMPTION OF PAN-FRIED MEATS - POSSIBLE MODULATION BY CRUCIFEROUS VEGETABLES, GLUTATHIONE S-TRANSFERASE-M1, AND N-ACETYLTRANSFERASE-2

Epidemiological and experimental evidence indicates that consumption o f fried meats in conjunction with certain genotypes of phase I and II metabolism genes poses an elevated risk for colorectal cancer. Paralle l to this, the consumption of cruciferous vegetables is associated wit h a reduced risk of colon cancer. Therefore, we designed a 6-week pilo t feeding study to evaluate the effect of these variables on urinary m utagenicity, which is a biomarker associated with fried-meat consumpti on. Eight subjects were fed fried meats daily for six weeks; four ate cruciferous vegetables, and four ate non-cruciferous vegetables, Urina ry mutagenicity was evaluated in the presence of S9 in strain YG1024 o f Salmonella, which is a frameshift strain that overproduces acetyltra nsferase. C18/methanol extracts of 24-h urines collected once each wee k were tested unhydrolyzed (free mutagenicity) and hydrolyzed (total m utagenicity); the difference between the two was the conjugated mutage nicity. Although not significant, the levels of conjugated urinary mut agenicity doubled among crucifera consumers and decreased to 30% of th e initial levels among non-crucifera consumers, suggesting the possibi lity that crucifera may enhance the level of conjugated urinary mutage nicity resulting from consumption of fried meats. Such an effect would be consistent with the documented ability of cruciferous vegetables t o induce phase II enzymes. The NAT2 rapid phenotype was significantly associated with similar to 2-fold increases in conjugated(p = 0.05) an d total (p = 0.004) urinary mutagenicity relative to NAT2 slow subject s, consistent with the elevated risk confirmed by the NAT2 rapid pheno type for colorectal cancer among meat consumers, An similar to 2-fold increase in urinary mutagenicity among the GSTMI(-) subjects relative to the GSTM1(+) subjects approached significance for free (p = 0.18) a nd total (p = 0.13) urinary mutagenicity. This is the first report on (a) the mutagenicity of hydrolyzed urine, which was consistently more mutagenic than unhydrolyzed urine; (b) the potential enhancement of co njugated urinary mutagenicity by crucifera; and (c) the association of the rapid NAT2 and possibly the GSTM1(-) phenotype with elevated leve ls of fried meat-associated urinary mutagenicity. (C) 1997 Elsevier Sc ience B.V.