Comparative toxicity of arsenite metabolites in wild type cho cells and in cells deficient in excision repair cross-complementing 1 and 2

• Published in: Toxicology in vitro 2008-09, Vol.22 (6), p.1662-1665
• Main Authors: Vahidnia, A., Pablo, R.F., van der Voet, G.B., van der Straaten, R.J.H.M., de Wolff, F.A.
• Format: Article
• Language: English
• Subjects: Animals; Arsenite and arsenate metabolites; Arsenites - administration & dosage; Arsenites - chemistry; Arsenites - toxicity; Calcium - metabolism; CHO Cells; Cricetinae; Cricetulus; DNA-Binding Proteins - drug effects; DNA-Binding Proteins - metabolism; Endonucleases - drug effects; Endonucleases - metabolism; Environmental Pollutants - administration & dosage; Environmental Pollutants - chemistry; Environmental Pollutants - toxicity; ERCC1; ERCC2; Humans; Hydrogen peroxide; Hydrogen Peroxide - metabolism; Lethal Dose 50; Xeroderma Pigmentosum Group D Protein - drug effects; Xeroderma Pigmentosum Group D Protein - metabolism
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2008.06.005

Arsenic (As) has been shown to alter one or more DNA repair processes. Excision repair cross-complementing 1 and 2 (ERCC1 and ERCC2) have shown to be associated with arsenic-induced toxicity and carcinogenicity. In this study, we investigated cytotoxic effects of various As metabolites in relation to two nucleotide excision repair genes: ERCC1 and ERCC2. Various arsenate (pentavalent) and arsenite (trivalent) metabolites were tested in ERCC1, ERCC2 deficient and wild type cells. Our results showed that in the selected concentration range pentavalent As metabolites; iAs V, MMA V and DMA V were not cytotoxic, unlike the trivalent As metabolites; iAs III, MMA III and DMA III. The measured LC 50 demonstrated a significant difference ( p < 0.01) for iAs III between the three cell lines, while MMA III and DMA III are more cytotoxic to all three cell lines. UV5 (ERCC2 deficient) cells also showed a lower resistance to iAs III in comparison to AA8 (wild type) and UV20 (ERCC2 deficient) cells. This might be explained through the generation of hydrogen peroxide (H 2O 2), which is generated by increase of intracellular Ca 2+ level. Generation of H 2O 2 in UV5 cells after incubation with iAs III is significantly higher than AA8 and UV20 cells ( p < 0.01). In conclusion, absence of ERCC2 leads to a increased generation of H 2O 2 by iAs III in UV5 cells, which is in contrast to AA8 and UV20 cells.