Carcinogenic Cr(VI) and the nutritional supplement Cr(III) induce DNA deletions in yeast and mice

Abstract

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 pun reversion assay in C57BL/6J p un/pun 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. ©2006 American Association for Cancer Research.