Induction of sister chromatid exchange by acrylamide and glycidamide in human lymphocytes: Role of polymorphisms in detoxification and DNA-repair genes in the genotoxicity of glycidamide

Autor: Nuno G. Oliveira, Célia Martins, José Rueff, João Pereira de Lima, Bruno Gomes, Marta Pingarilho, Jorge F. Gaspar, Vanda Martins, Anatalia Labilloy, Ana Sofia Fernandes
Rok vydání: 2013
Předmět:
Zdroj: Mutation Research/Genetic Toxicology and Environmental Mutagenesis. 752:1-7
ISSN: 1383-5718
DOI: 10.1016/j.mrgentox.2012.12.013
Popis: Acrylamide (AA) is a probable human carcinogen generated in carbohydrate-rich foodstuffs upon heating. Glycidamide (GA), formed via epoxidation, presumably mediated by cytochrome P450 2E1, is considered to be the active metabolite that plays a central role in the genotoxicity of AA. The aim of this work was to evaluate the cytogenetic damage induced by AA and GA in cultured human lymphocytes by use of the sister chromatid exchange (SCE) assay. Furthermore, this report addresses the role of individual genetic polymorphisms in key genes involved in detoxification and DNA-repair pathways (BER, NER, HRR and NHEJ) on the induction of SCE by GA. While AA induced the number of SCE/metaphase only slightly, especially for the highest concentration tested (2000 μM), GA markedly induced SCEs in a concentration-dependent manner up to concentrations of 750 μM, leading to an increase in SCEs of up to about 10-fold compared with controls. By combining DNA damage in GA-treated lymphocytes and data on polymorphisms, associations between the induction of SCEs with GSTP1 (Ile105Val) and GSTA2 (Glu210Ala) genotypes are suggested.
Databáze: OpenAIRE
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