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Perspectives
Killing of Chromium-Damaged Cells by Mismatch Repair and its Relevance to Carcinogenesis
Anatoly Zhitkovich, Elizabeth Peterson-Roth and Mindy Reynolds
volume 4 | issue 8
august 2005Pages: 1050-1052
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Hexavalent chromium compounds are widespread environmental contaminants that are well recognized as human carcinogens and potent respiratory toxicants. Intracellular metabolism of chromium(VI) leads to the production of numerous chromium-DNA adducts that are primarily formed at the phosphate groups. The mechanism of toxicity of these DNA modifications in human cells has been uncertain for a long time because chromium and other phosphate-based adducts did not block DNA replication with purified polymerases. Our recent studies identified mismatch repair proteins as activators of toxic responses to chromium-DNA damage, which resolved an apparent discrepancy in genotoxic activity of chromium adducts in cells and in vitro. The discovered mechanism of toxicity provided the basis for a novel model of chromium carcinogenesis based on the selection of resistant clones that lack mismatch repair and progress to cancer due to high levels of spontaneous mutagenesis.
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.