{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T12:55:04Z","timestamp":1761310504384,"version":"build-2065373602"},"reference-count":52,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2008,7,10]],"date-time":"2008-07-10T00:00:00Z","timestamp":1215648000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Applied Toxicology"],"published-print":{"date-parts":[[2008,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Hexavalent chromium [Cr(VI)] compounds are Group\u2010I human carcinogens. Cr(VI)\u2010induced DNA\u2013protein crosslinks (DPCs) have been implicated in the mutagenic and carcinogenic effects of Cr(VI). Although multiple mechanisms have been suggested for Cr(VI)\u2010induced DNA\u2013protein crosslinking, the mechanism of formation of DNA\u2013protein crosslinks is not well understood. In this study, we explored the hypothesis that Cr(VI)\u2010induced DPCs could be formed via generation of protein carbonyls and malonaldehyde (MDA) through protein oxidation and lipid peroxidation, respectively. Treatment of human leukemic T\u2010lymphocyte MOLT4 cells with potassium chromate induced the formation of protein carbonyls and DPCs within 2\u00a0h, but increased the level of MDA only after 4\u00a0h, in a dose\u2010dependent manner. Chromate treatment of MOLT4 cell homogenates also resulted in increased formation of MDA and protein carbonyls in a dose\u2010dependent manner. EPR spectrometry in combination with spin trapping techniques revealed that reaction of Cr(VI) with biological reductants such as NADPH, glutathione reductase or H<jats:sub>2<\/jats:sub>O<jats:sub>2<\/jats:sub> generates Cr(V) and <jats:sup>\u2022<\/jats:sup>OH radicals. Pretreatment of cells with antioxidants such as <jats:italic>\u03b1<\/jats:italic>\u2010tocopherol or Tiron inhibited chromate\u2010induced increase in formation of protein carbonyls, MDA and DPCs, but pretreatment of cells with riboflavin or 3\u2010aminotriazole, a catalase inhibitor, had the opposite effect. Our results, for the first time, demonstrate that Cr(VI) exposure increases the cellular level of protein carbonyls and that Cr(VI)\u2010induced DPCs may be formed, at least in part, via generation of protein carbonyls. Copyright \u00a9 2008 John Wiley &amp; Sons, Ltd.<\/jats:p>","DOI":"10.1002\/jat.1364","type":"journal-article","created":{"date-parts":[[2008,7,10]],"date-time":"2008-07-10T03:56:21Z","timestamp":1215662181000},"page":"987-997","source":"Crossref","is-referenced-by-count":24,"title":["Carcinogenic chromium(VI)\u2010induced protein oxidation and lipid peroxidation: implications in DNA\u2013protein crosslinking"],"prefix":"10.1002","volume":"28","author":[{"given":"Subhendra N.","family":"Mattagajasingh","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bhaba R.","family":"Misra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hara P.","family":"Misra","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2008,7,10]]},"reference":[{"key":"e_1_2_1_2_1","unstructured":"Agency for Toxic Substancesand Disease Registry.1993. 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