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URINARY MUTAGENICITY: A BIOMARKER OF GENOTOXIC EXPOSURES VIA AIR, WATER, AND DIET
Citation:
DEMARINI, D. M. URINARY MUTAGENICITY: A BIOMARKER OF GENOTOXIC EXPOSURES VIA AIR, WATER, AND DIET. Presented at 2007 Toxicology and Risk Assessment Conference, Cincinnati, OH, April 20 - 24, 2007.
Description:
During the past 30 years, ~100 studies have evaluated human urine for mutagenic activity using the Salmonella (Ames) mutagenicity assay. Urinary mutagenicity has been shown to correlate well with other biomarkers, including DNA and hemoglobin adducts, urinary metabolites, and chromosomal aberrations or micronuclei in peripheral blood lymphocytes. Urinary mutagenicity has the advantage of providing an integrated measure of exposure to a complex mixture of genotoxins. However, identification of the genotoxins in the urine requires fractionation and analytical studies. Genotoxic exposures can result in urinary mutagenicity a few hours after initial exposure and may be detectable up to 12 or even 24 hours afterwards. We have coupled an acid-hydrolysis procedure with C18/methanol extraction to identify conjugated vs. unconjugated urinary mutagenicity. We showed in a clinical case-control study of patients with colorectal polyps, which are potential precursors to colon cancer, that the un-conjugated urinary mutagenicity was predictive of risk for colorectal polyps. We have shown that urinary mutagenicity correlates with a variety of other biomarkers in subjects exposed to cigarette smoke, benzidine dyes, DNT or TNT, wood smoke, and well-cooked pan-fried meat. Our studies have demonstrated that dietary interventions, such as consumption of cruciferous vegetables, can reduce the levels of urinary mutagenicity as well as other biomarkers of exposure. We have shown that dermal exposure to bromodichloromethane, a common mutagen in chlorinated drinking water, produces more urinary mutagenicity than oral exposure to this disinfection by-product. Meta-analysis (Lin et al., Occupat. Environ. Med. 62:750, 2005) found that a variety of biomarkers, including urinary mutagenicity, correlated well with each other but not with external measures of exposure, such as concentrations of a compound in the air or on the skin. Thus, biomarkers appear to be more robust measures of exposure than external analytical measurements of single compounds.