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URINARY MUTAGENESIS AS AN EXPOSURE BIOMARKER OF COOKED-MEAT-ASSOCIATED MUTAGENS: INFLUENCE OF COOKING TEMPERATURE, PHENOTYPE, AND GENOTYPE IN A CONTROLLED METABOLIC FEEDING STUDY
Citation:
Peters, U., R. Sinha, D. A. Bell, D. J. Grant, D M. DeMarini, M. A. Watson, M. Kulldorff, N. Rothman, L R. Brooks, AND S H. Warren. URINARY MUTAGENESIS AS AN EXPOSURE BIOMARKER OF COOKED-MEAT-ASSOCIATED MUTAGENS: INFLUENCE OF COOKING TEMPERATURE, PHENOTYPE, AND GENOTYPE IN A CONTROLLED METABOLIC FEEDING STUDY. ENVIRONMENTAL AND MOLECULAR MUTAGENESIS 43(1):53-74, (2004).
Description:
ABSTRACT
We evaluated urinary mutagenicity and selected phenotypes and genotypes in 60 subjects in a metabolic feeding study in which meat cooked at low temperature (100oC) was consumed for 1 week followed by meat cooked at high temperature (250oC) the second week. Meat cooked at 100oC was not mutagenic and had no detectable levels of heterocyclic amines (HCAs), whereas meat cooked at 250oC was mutagenic and had appreciable levels of HCAs. Levels of polycyclic aromatic hydrocarbons (PAHs) in the meat were low and similar during both weeks. Compared to subjects who consumed meat cooked at 100oC, those who consumed meat cooked at 250oC had unhydrolyzed or acid-hydrolyzed urine that was 22-131X more mutagenic, respectively. Meat intake correlated with the mutagenicity of unhydrolyzed (r = 0.32, P = 0.01) and hydrolyzed (r = 0.34, P = 0.008) urine. Urinary mutagenicity paralleled levels of HCAs but not levels of PAHs in the meat, indicating that HCAs are a primary cause of cooked-meat-associated urinary mutagenicity. The levels of mutagenicity and MeIQx correlated in unhydrolyzed urine (r = 0.36, P = 0.01), and the levels of mutagenicity and MeIQx (r = 0.34, P = 0.01) or mutagenicity and PhIP (r = 0.43, P = 0.001) correlated in hydrolyzed urine. Thus, acid-hydrolysis de-conjugated mutagens, explaining our finding that hydrolyzed urine was ~8X more mutagenic than unhydrolyzed urine. Urinary mutagenicity was not influenced by either CYP1A2 or NAT2 phenotypes or CYP1A1, NAT1, or NAT2 genotypes. However, a UGT1A1*28 polymorphism that reduces UGT1A1 expression and conjugation resulted in higher levels of urinary mutagenicity (unhydrolyzed) relative to those without this allele (P = 0.04). This study demonstrates that urinary mutagenicity is a biomarker of exposure of cooked-meat-associated mutagenicity, due largely to HCAs, and should be useful in exposure assessment of cooked-meat-associated cancer.