Arsenite enhances the benzo[a]pyrene diol epoxide (BPDE)-induced mutagenesis with no marked effect on repair of BPDE-DNA adducts in human lung cells

• Published in: Toxicology in vitro 2009-08, Vol.23 (5), p.897-905
• Main Authors: Chiang, Huai-chih, Tsou, Tsui-Chun
• Format: Article
• Language: English
• Subjects: 7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide - toxicity; Arsenic; Arsenites - toxicity; Benzo[a]pyrene; Cell Line; Cell Line, Tumor; DNA Adducts - toxicity; Drug Synergism; Genes, Suppressor; Humans; Lung - cytology; Lung - drug effects; Lung - metabolism; Lung cancer; Lung Neoplasms - metabolism; Mutagenesis; Mutagenesis - drug effects; Mutagens - toxicity; Mutation - drug effects; p53; RNA, Transfer - genetics; Simian virus 40; Sodium Compounds - toxicity; Tumor Suppressor Protein p53 - metabolism
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2009.05.009

Arsenite effects on the benzo[a]pyrene diol epoxide (BPDE)-DNA adduct-induced mutation were evaluated in three human lung cell-lines – A549 (wild-type p53), WI38-VA13 (p53 inhibited by SV40 large-T antigen), and H1299 (p53-null) – by using the pSP189 shuttle vector, which carries a mutation target supF gene. Arsenite alone had no significant effect on the spontaneous supF mutation. BPDE modification of pSP189 enhanced the mutation rates of supF 4.37-fold, 2.96-fold, and 1.95-fold for A549, WI38-VA13, and H1299, respectively. Arsenite potentiated the BPDE-induced mutation rates of supF 2.30-fold, 2.31-fold, and 2.35-fold in A549, WI38-VA13, and H1299, respectively. These results suggest that arsenite potentiates the BPDE-induced supF mutation via a p53-independent mechanism. By using the host cell reactivation assay, we evaluated arsenite effect on repair of BPDE-DNA adducts. We found that the arsenite treatments resulting in relative survival rates ⩾65% had no significant effect on repair of BPDE-DNA adducts, indicating that p53 status did not significantly affect the repair of BPDE-DNA adducts. This study reveals that arsenite enhances the BPDE-DNA adduct-induced mutagenesis with no marked effect on repair of BPDE-DNA adducts, suggesting that arsenic may act as a co-mutagen to promote the development of human lung cancer.