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Polymorphic trial in oxidative damage of arsenic exposed Vietnamese

Journal Article · · Toxicology and Applied Pharmacology
 [1];  [2];  [3];  [2];  [4]; ;  [5];  [1]
  1. Department of Legal Medicine, Faculty of Medicine, Shimane University, Izumo, Shimane (Japan)
  2. Department of Forensic Medicine and Human Genetics, Kurume University School of Medicine, Kurume, Fukuoka (Japan)
  3. Division of Medical Genetics and Biochemistry, Faculty of Medical Sciences, University of Fukui, Eiheiji-cho, Fukui (Japan)
  4. Department of Environmental Sciences, Faculty of Science, Shinshu University, Matsumoto, Nagano (Japan)
  5. Center for Marine Environmental Studies (CMES), Ehime University, Matsuyama Ehime (Japan)

Arsenic causes DNA damage and changes the cellular capacity for DNA repair. Genes in the base excision repair (BER) pathway influence the generation and repair of oxidative lesions. Single nucleotide polymorphisms (SNPs) in human 8-oxoguanine DNA glycosylase (hOGG1) Ser326Cys; apurinic/apyrimidinic endonuclease (APE1) Asp148Glu; X-ray and repair and cross-complementing group 1 (XRCC1) Arg280His and Arg399Gln in the BER genes were analyzed, and the relationship between these 4 SNPs and the urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) concentrations of 100 Vietnamese population exposed to arsenic was investigated. Individuals with hOGG1 326Cys/Cys showed significantly higher urinary 8-OHdG concentrations than did those with 326 Ser/Cys and Ser/Ser. As for APE1 Asp148Glu, heterozygous subjects showed significantly higher urinary 8-OHdG concentrations than did those homozygous for Asp/Asp. Moreover, global ethnic comparison of the allelic frequencies of the 4SNPs was performed in 10 population and previous reported data. The mutant allele frequencies of hOGG1 Ser326Cys in the Asian populations were higher than those in the African and Caucasian populations. As for APE1 Asp148Glu, Caucasians showed higher mutant frequencies than those shown by African and Asian populations. Among Asian populations, the Bangladeshi population showed relatively higher mutant allele frequencies of the APE1 Asp148Glu polymorphism. This study is the first to demonstrate the existence of genetic heterogeneity in a worldwide distribution of SNPs (hOGG1 Ser326Cys, APE1 Asp148Glu, XRCC1 Arg280His, and XRCC1 Arg399Gln) in the BER genes. - Highlights: > We showed that hOGG1 and APE1 are associated with urinary 8-OHdG concentrations. > We showed the existence of inter-ethnic differences in hOGG1 and APE1 polymorphism. > These polymorphisms is a genetic marker of susceptibility to oxidative stress.

OSTI ID:
21587862
Journal Information:
Toxicology and Applied Pharmacology, Journal Name: Toxicology and Applied Pharmacology Journal Issue: 2 Vol. 256; ISSN TXAPA9; ISSN 0041-008X
Country of Publication:
United States
Language:
English