Impact of sodium arsenite on chromosomal aberrations with respect to polymorphisms of detoxification and DNA repair genes.
Arsenic compounds can increase production of reactive oxygen species. Reactive oxygen species can induce double-strand breaks in DNA, which is a cause of chromosome aberrations (CAs). This study was conducted to determine the association between arsenic exposure and polymorphisms of genes involved in detoxification (glutathione S-transferase T1 [GSTT1], glutathione S-transferase M1 [GSTM1], glutathione S-transferase O2 [GSTO2], catalase [CAT], and NAD(P)H quinone oxidoreductase1 [NQO1]) as well as nonhomologous end joining DNA repair genes (XRCC4, XRCC5, and XRCC6) with induction of chromosomal aberrations. The participants consisted of 123 healthy males who were genotyped using polymerase chain reaction-based methods. Primary cultures of whole blood were treated with sodium arsenite (NaAsO(2); iAs(III); at final concentration 1 µmol/L), mitomycin C (at final concentration 60 ηg/mL; as positive control), or untreated. For each culture, mitotic index (MI), chromatid breaks (CBs), CAs, and total percentage of aberrant cells were determined. The levels of CB and percentage of aberrant cells were significantly higher in the TT genotype of CAT (C-262T polymorphism) than the CC genotype. The CB value in samples with GSTM1 active genotype was significantly higher than the null genotype. The MI in samples with TT genotype of NQO1 (C609T polymorphism) was significantly higher than MI in samples having CC and CT genotypes. There was no association between MI, CB, CA, and percentage of aberrant cells and polymorphisms of XRCC4, XRCC5, and XRCC6.
Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran Institute of Biotechnology, Shiraz University, Shiraz, Iran.
Fatemeh
F
Azizian-Farsani
Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran Institute of Biotechnology, Shiraz University, Shiraz, Iran.
Gholamreza
G
Rafiei
Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran Institute of Biotechnology, Shiraz University, Shiraz, Iran saadat@shirazu.ac.ir.
Mostafa
M
Saadat
D000328:Adult; D034961:Antigens, Nuclear / Q000235:genetics; D018053:Arsenites / Q000633:toxicity*; D002374:Catalase / Q000235:genetics*; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000139:chemically induced*; D004265:DNA Helicases / Q000235:genetics; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D005982:Glutathione Transferase / Q000235:genetics*; D006801:Humans; D000072200:Ku Autoantigen; D008297:Male; D008875:Middle Aged; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics*; D011110:Polymorphism, Genetic; D017670:Sodium Compounds / Q000633:toxicity*; D055815:Young Adult
D034961:Antigens, Nuclear; D018053:Arsenites; D002374:Catalase; D004265:DNA Helicases; D004268:DNA-Binding Proteins; D005982:Glutathione Transferase; D000072200:Ku Autoantigen; D016660:NAD(P)H Dehydrogenase (Quinone); D017670:Sodium Compounds; C101467:XRCC4 protein, human; C017947:sodium arsenite; C577219:CAT protein, human; C447479:NQO1 protein, human; C413545:glutathione S-transferase T1; C492569:GSTO2 protein, human; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human
DNA repair; cell culture; detoxification; polymorphism; sodium arsenite