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Inhibition of arsenite methylation induces synergistic genotoxicity of arsenite and benzo(a)pyrene diol epoxide in SCC-7 cells

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Abstract

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.

Graphical abstract: Inhibition of arsenite methylation induces synergistic genotoxicity of arsenite and benzo(a)pyrene diol epoxide in SCC-7 cells

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Publication details

The article was received on 30 Jul 2018, accepted on 29 Oct 2018 and first published on 30 Oct 2018


Article type: Paper
DOI: 10.1039/C8MT00217G
Citation: Metallomics, 2019, Advance Article
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    Inhibition of arsenite methylation induces synergistic genotoxicity of arsenite and benzo(a)pyrene diol epoxide in SCC-7 cells

    Y. Li, M. He, B. Chen and B. Hu, Metallomics, 2019, Advance Article , DOI: 10.1039/C8MT00217G

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