Genetic Polymorphisms in Detoxification and DNA Repair Genes and Susceptibility to Glycidamide-Induced DNA Damage

Abstract

Acrylamide (AA) is a probable human carcinogen formed in carbohydrate-rich foodstuffs upon heating. Glycidamide (GA), the AA metabolite formed by epoxidation, is considered the ultimate genotoxic agent. In this study, the in vitro genotoxic potential of AA and GA in human whole blood leukocytes was compared using the alkaline comet assay. Although AA did not induce significant DNA damage in the concentrations tested (up to 1000 μM), GA markedly increased the percentage of tail DNA at concentrations ≥250 μM. Further, this study addressed the role of genetic polymorphisms in key genes involved in metabolism and DNA repair pathways (BER, NER, HRR, and NHEJ) on GA-induced genotoxicity assessed by the alkaline comet assay. The results obtained suggested associations between DNA damage and polymorphisms of BER (MUTYH Gln335His and XRCC1 Gln399Arg) and NER (XPC Ala499Val and Lys939Gln) genes, either alone or in combination.

Acknowledgments

This work was supported by the Center for Research in Human Molecular Genetics (CIGMH), projects PTDC/SAU-OSM/105572/2008, PTDC/SAU-ESA/102367/2008, and PTDC/QUI/67522/2006 from Fundação da Ciência e Tecnologia (FCT), and Fundação Calouste Gulbenkian (grant 76438/2006). The grants to M. Pingarilho (SFRH/BD/22612/2005) and A. S. Fernandes (SFRH/BPD/69042/2010) from FCT are also acknowledged.