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

• Published in: Mutation research. Genetic toxicology and environmental mutagenesis 2013-04, Vol.752 (1-2), p.1-7
• Main Authors: Pingarilho, Marta, Oliveira, Nuno G., Martins, Célia, Gomes, Bruno Costa, Fernandes, Ana Sofia, Martins, Vanda, Labilloy, Anatália, de Lima, João Pereira, Rueff, José, Gaspar, Jorge Francisco
• Format: Article
• Language: English
• Subjects: Acrylamide; Carbohydrates; Carcinogens; Detoxification; DNA repair; DNA-repair polymorphisms; Genotype & phenotype; Glycidamide; Lymphocytes; Metabolites; Polymorphism; Sister chromatid exchange
• ISSN: 1383-5718; 1879-3592
• DOI: 10.1016/j.mrgentox.2012.12.013

► DNA damage induced by AA and GA in cultured human lymphocytes was evaluated. ► AA only slightly induced SCEs, especially for the highest concentration tested. ► GA markedly induced SCEs in a dose–response manner up to 750μM. ► Associations between the induction of SCEs with GSTP1 and GSTA2 polymorphisms are suggested. 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 (2000μM), GA markedly induced SCEs in a concentration-dependent manner up to concentrations of 750μM, 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.