The ERCC2/XPD Lys751Gln polymorphism affects DNA repair of benzo[a]pyrene induced damage, tested in an in vitro model. (August 2016)

• Record Type: Journal Article
• Authors: Xiao, Sha; Cui, Su; Lu, Xiaobo; Guan, Yangyang; Li, Dandan; Liu, Qiufang; Cai, Yuan; Jin, Cuihong; Yang, Jinghua; Wu, Shengwen; van der Straaten, Tahar
• Is Part Of: Toxicology in vitro. Volume 34(2016)
• Page Start: 300
• Page End: 308
• Publication Date: 2016-08
• Subjects: ERCC2/XPD Lys751Gln -- Nucleotide excision repair (NER) -- DNA repair capacity -- Benzo[a]pyrene (B[a]P) -- Cancer development; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2016.04.015
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: Nucleotide excision repair (NER) is an important defense mechanism of the body to exogenous carcinogens and mutagens, such as benzo[a]pyrene (B[a]P). Genetic polymorphisms in ERCC2/XPD, a critical element in NER, are thought to be associated with individual's cancer susceptibility. Although ERCC2/XPD Lys751Gln (rs13181) is the most studied polymorphism, the impact of this polymorphism on DNA repair capacity to carcinogen remains unclear. In the present study, cDNA clones carrying different genotypes of ERCC2/XPD (Lys751Gln) were introduced into an ERCC2/XPD deficient cell line (UV5) in a well-controlled biological system. After B[a]P treatment, cell growth inhibition rates and DNA damage levels in all cells were detected respectively. As expected, we found that the DNA repair capacity in UV5 cells was restored to levels similar to wildtype parent AA8 cells upon introduction of the cDNA clone of ERCC2/XPD (Lys751). Interestingly, after B[a]P treatment, transfected cells expressing variant ERCC2/XPD (751Gln) showed an enhanced cellular sensitivity and a diminished DNA repair capacity. The wildtype genotype AA (Lys) was found to be associated with a higher DNA repair capacity as compared to its polymorphic genotype CC (Gln). These data indicate that ERCC2/XPD Lys751Gln polymorphism affects DNA repair capacity after exposure to environmental carcinogens such as B[a]P in this well-controlled in vitro system and could act as a biomarker to increase the predictive value to develop cancer. Highlights: An in vitro cell model was used to detect the difference of ERCC2/XPD Lys751Gln SNP. Genotype AA of the SNP was found to be associated with a higher DNA repair to B[a]P. ERCC2/XPD Lys751Gln could increase the predictive value of cancer susceptibility. A well controlled in vitro cell model contributed to study the function of a SNP.