TOXI 102 |
| Cancer formation in humans following exposure to the hexavalent oxidation state of chromium has been recognized for over 100 years but its mechanism of initiation is still poorly understood. Two putative pathways, an oxidative and binding pathway, have been proposed to account for the mechanism of cancer induction by chromium. The research in our lab focuses on understanding the oxidative pathway of chromium-induced DNA damage as it relates to the formation of base-specific lesions. We have found that oxidation of DNA by Cr(VI) forms a series of “further oxidized” lesions of guanine identified as spiroiminodihydantoin (Sp) and guanidinohydantoin (Gh). These lesions have been identified arising from chromium oxidation both in vitro and in cellular systems. The relative levels of these “further oxidized” lesions of guanine were found to be significantly greater than the “ubiquitous” 8-oxo-dG lesion. The formation of Sp and Gh lesions in these systems has implications for the carcinogenicity of chromate as they are significantly more mutagenic than the 8-oxo-dG lesion. |
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Metal Carcinogenesis: New Concepts
2:00 PM-5:00 PM, Wednesday, 13 September 2006 Moscone Center -- Room 308, Oral
Division of Chemical Toxicology |