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Toxicol In Vitro. 2016 Aug;34:123-127. doi: 10.1016/j.tiv.2016.03.018. Epub 2016 Apr 5.

Glycidamide genotoxicity modulated by Caspases genes polymorphisms.

Author information

1
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.
2
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.

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.

KEYWORDS:

Acrylamide; Apoptosis; Cancer susceptibility; Caspases genes polymorphisms; DNA damage; Glycidamide

PMID:
27062911
DOI:
10.1016/j.tiv.2016.03.018
[Indexed for MEDLINE]

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