title: Glycidamide genotoxicity modulated by Caspases genes polymorphisms.
abstract: Acrylamide (AA) is amongst acknowledged carcinogenic dietary factors. Its DNA-reactive metabolite is glycidamide (GA). The present study intended to correlate the role of key polymorphic genes of apoptosis (CASP7, CASP8, CASP9, CASP10, LTA and TNFRSF1B) with biomarkers of effect of DNA damage, namely the sister chromatid exchange assay (SCE) and the comet assay in whole blood cells exposed to GA. The aim was to assess as a proof of concept the role that pro-apoptotic effector proteins might have in the yields of genotoxic effects when those effector proteins are coded by polymorphic genes. Whole blood from a small group of volunteers was exposed to GA to assess DNA damage and the volunteers were genotyped for polymorphic genes related to apoptosis pathways. A relation between the induction of SCE and several variants of the polymorphism CASP8 rs1035142 G>T was observed. Also, a relation between the % tail DNA and the CASP10 I522L polymorphism was found. Furthermore, associations between % tail DNA and several SNP-SNP interactions of CASP8 and CASP10 were found. A possible correlation between DNA damage and the genetic susceptibility, bestowed by polymorphic genes in the apoptosis inducing pathways was verified.
authors.affiliation: Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Rua Câmara Pestana, 6, 1150-082 Lisboa, Portugal.
authors.forename: João Pereira
authors.initials: JP
authors.lastname: de Lima
authors.affiliation: Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Rua Câmara Pestana, 6, 1150-082 Lisboa, Portugal.
authors.forename: Susana N
authors.initials: SN
authors.lastname: Silva
authors.affiliation: Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Rua Câmara Pestana, 6, 1150-082 Lisboa, Portugal.
authors.forename: José
authors.initials: J
authors.lastname: Rueff
authors.affiliation: Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, NOVA Medical School/Faculdade de Ciências Médicas, Universidade Nova de Lisboa, Rua Câmara Pestana, 6, 1150-082 Lisboa, Portugal; Global Health and Tropical Medicine, GHTM, Instituto de Higiene e Medicina Tropical, IHMT, Universidade Nova de Lisboa, Rua da Junqueira 100, 1349-008 Lisboa, Portugal. Electronic address: martapingarilho@ihmt.unl.pt.
authors.forename: Marta
authors.initials: M
authors.lastname: Pingarilho
mesh_terms: D020169:Caspases / Q000235:genetics*; D002478:Cells, Cultured; D020552:Comet Assay; D004249:DNA Damage; D004852:Epoxy Compounds / Q000633:toxicity*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects / Q000378:metabolism; D009153:Mutagens / Q000633:toxicity*; D011110:Polymorphism, Genetic; D012854:Sister Chromatid Exchange
chemical_list: D004852:Epoxy Compounds; D009153:Mutagens; C071834:glycidamide; D020169:Caspases
keywords: Acrylamide; Apoptosis; Cancer susceptibility; Caspases genes polymorphisms; DNA damage; Glycidamide