Inhibition of arsenite methylation induces synergistic genotoxicity of arsenite and benzo(a)pyrene diol epoxide in SCC-7 cellsElectronic supplementary information (ESI) available. See DOI: 10.1039/c8mt00217g

As is well-known, arsenite (As( iii )) is a human carcinogen associated with many human cancers. As( iii ) can act as a co-carcinogen to induce DNA damage with other carcinogens. Benzo( a )pyrene diol epoxide (BPDE) is one of the most-studied environmental carcinogens, which exists ubiquitously in our daily life. The elucidation of the mechanism of As( iii ) as a co-carcinogen with BDPE in cells causing genotoxicity is beneficial for the evaluation of its bioeffect. In this study, a comprehensive analytical system is used for DNA damage evaluation, BPDE-DNA adduct detection, arsenic speciation and gene expression analysis. Based on the experimental results, it can be inferred that BPDE and As( iii ) synergistically cause genotoxicity, and the possible mechanism is that BPDE inhibits arsenic methylation, leading to cellular As( iii ) enrichment. As( iii ) inhibits nucleotide excision repair (NER) of the DNA adduct damage caused by BPDE. The synergistic effect of BPDE and As( iii ) causes DNA strand break damage, which further results in carcinogenesis. A comprehensive analytical method was developed to investigate the synergistic genotoxicity of BPDE and As( iii ) in SCC-7 cells.