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Carcinogenic Cr(VI) and the Nutritional Supplement Cr(III) Induce DNA Deletions in Yeast and Mice

Departments of Pathology, Environmental Health, and Radiation Oncology, Geffen School of Medicine and School of Public Health, University of California at Los Angeles, Los Angeles, California

Requests for reprints: Robert H. Schiestl, Department of Pathology, University of California at Los Angeles School of Medicine, 650 Charles E. Young Drive South, Los Angeles, CA 90095. Phone: 310-267-2087; Fax: 310-267-2578; E-mail: rschiestl{at}mednet.ucla.edu.

Industrial Cr(VI) emissions contaminate drinking water sources across the U.S., and many people take Cr(III) nutritional supplements. Cr(VI) is a human pulmonary carcinogen, but whether it is carcinogenic in the drinking water is not known. Due to widespread human exposure, it is imperative to determine the carcinogenic potential of Cr(VI) and Cr(III). DNA deletions and other genome rearrangements are involved in carcinogenesis. We determined the effects of Cr(VI) as potassium dichromate and Cr(III) as chromium(III) chloride on the frequencies of DNA deletions measured with the deletion assay in Saccharomyces cerevisiae and the in vivo p^un reversion assay in C57BL/6J p^un/p^un mice. Exposing yeast and mice via drinking water to Cr(VI) and Cr(III) significantly increased the frequency of DNA deletions. We quantified intracellular chromium concentrations in yeast and tissue chromium concentrations in mice after exposure. Surprisingly, this revealed that Cr(III) is a more potent inducer of DNA deletions than Cr(VI) once Cr(III) is absorbed. This study concludes that both the environmental contaminant Cr(VI) and the nutritional supplement Cr(III) increase DNA deletions in vitro and in vivo, when ingested via drinking water. (Cancer Res 2006; 66(7): 3480-4)

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