Arsenite pretreatment attenuates benzo[a]pyrene cytotoxicity in a human lung adenocarcinoma cell line by decreasing cyclooxygenase-2 levels

Journal of Toxicology and Environmental Health. Part a
I-Ching Ho, Te-Chang Lee

Abstract

Both simultaneous and sequential exposure to arsenite and benzo[a]pyrene (BaP) potentially occur in human populations drinking arsenic-contaminated water or burning arsenic-contaminated coal. Although arsenite and BaP are both well-documented hazardous substances and human carcinogens, interactions between these two agents have not been well defined. In this study, we demonstrated that posttreatment with arsenite synergistically enhanced the cytotoxicity of BaP for a human lung adenocarcinoma cell line, CL3. In contrast, pretreatment of CL3 cells with arsenite attenuated BaP cytotoxicity. Involvement of heat-shock protein 70 and heme oxygenase-1 in this arsenite-mediated attenuation of BaP cytotoxicity was ruled out. Our data also indicated that arsenite pretreatment did not affect the BaP-mediated induction of CYP1A1, the initial enzyme involved in its metabolic activation, but did result in a significant decrease in mRNA and protein levels of cyclooxygenase-2 (COX-2), which is required to convert the BaP metabolite BaP 7,8-dihydrodiol to the ultimate epoxide. In contrast to the high susceptibility of CL3 cells to BaP, the human lung carcinoma cells, H460, and CL3R15 cells (arsenic-resistant CL3 cells) showed normal CYP1A1 ind...Continue Reading

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Citations

May 7, 2009·Expert Opinion on Drug Metabolism & Toxicology·Anwar Anwar-MohamedAyman Os El-Kadi
May 11, 2006·Drug Metabolism Reviews·Laurence Kaminsky
Dec 23, 2008·Toxicology in Vitro : an International Journal Published in Association with BIBRA·Zhi-Feng MiaoTsui-Chun Tsou
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Nov 10, 2016·Environmental Toxicology and Pharmacology·Adeel SattarZonghui Yuan
Dec 4, 2004·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Erin E BessetteLaurence S Kaminsky

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