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URINARY MUTAGENICITY AS A BIOMARKER OF COOKED-MEAT-ASSOCIATED MUTAGENS AND RISK FOR COLORECTAL ADENOMA
Citation:
DeMarini, D M., U. Peters, D. A. Bell, M. Kuldorff, S H. Warren, N. Rothman, AND R. Sinha. URINARY MUTAGENICITY AS A BIOMARKER OF COOKED-MEAT-ASSOCIATED MUTAGENS AND RISK FOR COLORECTAL ADENOMA. Presented at Environmental Mutagen Society, Miami Beach, FL, May 10-15, 2003.
Description:
Urinary Mutagenicity as a Biomarker of Cooked-Meat-Associated Mutagens and Risk for Colorectal Adenoma
In a controlled feeding study involving 60 subjects, we have investigated urinary mutagenicity as a biomarker of exposure to cooked-meat-associated mutagens. In a separate clinical-based, case-control study involving 299 subjects, we investigated urinary mutagenicity (Salmonella assay) and colorectal adenoma risk. For the feeding study, meat was cooked at low temperature (100oC) and 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. The levels of PAHs in the meat were similar during both weeks. Mutagenicity of unhydrolyzed and acid-hydrolyzed urine was 22X and 131X more mutagenic, respectively, when subjects consumed meat cooked at 250oC compared to meat cooked at 100oC. Urinary mutagenicity paralleled levels of HCAs but not levels of PAHs in the meat and in the urine, suggesting that HCAs are a primary cause of cooked-meat-associated urinary mutagenicity in this study. Neither CYP1A2 nor NAT2 phenotypes or CYP1A1, NAT1, or NAT2 genotypes influenced urinary mutagenicity. However, the UGT1A1*28 polymorphism significantly modified the effect of meat intake on urinary mutagenicity (multiplicative interaction P = 0.04). Thus, urinary mutagenicity is a biomarker of exposure to cooked-meat-associated mutagens. In the second study, urinary mutagenicity and colorectal adenoma risk were examined in 143 cases and 156 controls. Adenoma risk was 2.4-fold higher in subjects in the highest vs. lowest quintile of urinary mutagenicity (95% CI = 1.1-5.1). Combining urinary mutagenicity with previously estimated intake of meat-derived mutagenicity resulted in a 5.6-fold increase in adenoma risk (95% CI = 2.2-13.9, comparing highest to lowest quintile). Thus, in our study population, diet may contribute to mutagenic exposure, which was positively associated with colorectal adenoma risk. [Abstract does not necessarily reflect the policy of the US EPA.]