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• W2024244294 abstract "Inorganic arsenic (iAs) and its toxic methylated metabolite, methylarsonous acid (MMAIII), both have carcinogenic potential. Prior study shows iAs-induced malignant transformation in both arsenic methylation-proficient (liver) and methylation-deficient (prostate) cells, but only methylation-proficient cells show oxidative DNA damage (ODD) during this transformation. To further define whether arsenic methylation is necessary for transformation or ODD induction, here we chronically exposed these same liver or prostate cell lines to MMAIII (0.25–1.0 μM) and tested for acquired malignant phenotype. Various metrics of oncogenic transformation were periodically assessed along with ODD during chronic MMAIII exposure. Methylation-deficient and methylation-proficient cells both acquired a cancer phenotype with MMAIII exposure at about 20 weeks, based on increased matrix metalloproteinase secretion, colony formation, and invasion. In contrast, prior work showed iAs-induced transformation took longer in biomethylation-deficient cells (~30 weeks) than in biomethylation-proficient cells (~18 weeks). In the present study, MMAIII caused similar peak ODD levels at similar concentrations and at similar exposure times (18–22 weeks) in both cell types. At the approximate peak of ODD production, both cell types showed similar alterations in arsenic and oxidative stress adaptation factors (i.e., ABCC1, ABCC2, GST-π, SOD-1). Thus, MMAIII causes oncogenic transformation associated with ODD in methylation-deficient cells, indicating that further methylation is not required to induce ODD. Together, these results show that MMAIII and iAs cause an acquired malignant phenotype in methylation-deficient cells, yet iAs does not induce ODD. This indicates iAs likely has both genotoxic and non-genotoxic mechanisms dictated by the target cell’s ability to methylate arsenic." @default.
• W2024244294 created "2016-06-24" @default.
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• W2024244294 date "2013-10-05" @default.
• W2024244294 modified "2023-10-14" @default.
• W2024244294 title "Methylarsonous acid causes oxidative DNA damage in cells independent of the ability to biomethylate inorganic arsenic" @default.
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• W2024244294 doi "https://doi.org/10.1007/s00204-013-1141-2" @default.
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