title: 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.
abstract: 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.
authors: Department of Genetics, Faculty of Medical Sciences, Universidade Nova de Lisboa (CIGMH), Rua da Junqueira 100, 1349-008 Lisboa, Portugal. mpingarilho.gene@fcm.unl.pt
authors: Marta
authors: M
authors: Pingarilho
authors: Nuno G
authors: NG
authors: Oliveira
authors: Célia
authors: C
authors: Martins
authors: Bruno Costa
authors: BC
authors: Gomes
authors: Ana Sofia
authors: AS
authors: Fernandes
authors: Vanda
authors: V
authors: Martins
authors: Anatália
authors: A
authors: Labilloy
authors: João Pereira
authors: JP
authors: de Lima
authors: José
authors: J
authors: Rueff
authors: Jorge Francisco
authors: JF
authors: Gaspar
mesh_terms: D020106:Acrylamide / Q000633:toxicity*; D004249:DNA Damage; D004260:DNA Repair; D004852:Epoxy Compounds / Q000633:toxicity*; D051549:Glutathione S-Transferase pi / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D008658:Inactivation, Metabolic / Q000235:genetics; D007527:Isoenzymes / Q000235:genetics; D008214:Lymphocytes / Q000187:drug effects; D009153:Mutagens / Q000633:toxicity*; D011110:Polymorphism, Genetic; D012854:Sister Chromatid Exchange
chemical_list: D004852:Epoxy Compounds; D007527:Isoenzymes; D009153:Mutagens; D020106:Acrylamide; C071834:glycidamide; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha