Genotoxicity Of Trace Level Of Hexavalent Chromium Existing In City Water

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Tens of millions of Americans consume trace amounts of potentially toxic hexavalent chromium (Cr(VI)) through drinking city water every day. According to the studies conducted by the Environmental Working Group, 89% of the water samples from U.S. cities are contaminated with Cr(VI) at levels ranging from 0.03 to 12.9 μg/L. While trivalent chromium (Cr(III)) is among the essential trace elements for normal carbohydrate, lipid, and protein metabolism in humans, Cr(VI) has been extensively studied as a toxic heavy metal ion. Cr(VI) is a well-known human carcinogen by inhalation; in contrast, it is a rodent carcinogen by ingestion of extremely high doses (57,300 μg/L or higher) in drinking water. The United States Environmental Protection Agency (USEPA) and other regulatory agencies in the world have set the maximum contaminant levels (MCL) for total Cr or Cr(VI) in human drinking water at 50 or 100 μg/L, although the USEPA is currently re-evaluating these regulations. The mechanism by which Cr(VI) causes genotoxicity is well-characterized at concentrations equivalent to current regulatory levels or higher. The genotoxic mode of action of Cr(VI) appears to be due to the intracellular reduction of Cr(VI) to Cr(III) leading to the formation of a ternary complex between DNA, Cr(III), and intracellular reducing molecules. However, little information is available regarding the biological effects of Cr(VI) at doses lower than 100 μg/L. In this study, we investigated the effects of Cr(VI) at nanomolar ranges (1 μg/L or higher) on the DNA damage response in isogenic cultured cells deficient in various DNA repair genes. Here we show that the DNA damage response is observed after a three-day incubation with Cr(VI) at 2-5 μg/L (ppb), which is lower than the Cr(VI) concentrations detected in some of city water in the US. Strikingly, the genotoxicity of Cr(VI) decreased ∼3000 times depending on its incubation time, ranging from three days to ten minutes. Our dose- and time-dependent Cr(VI) genotoxicity results, combined with the estimated transit time of Cr(VI) in the digestive tracts of humans, strongly suggest that trace amounts of Cr(VI) in drinking water at levels 12.9 μg/L or lower are unlikely to cause a significant impact on inducing carcinogenicity in the oral cavity and small intestine. Citation Format: Xu Tian, Keyur Patel, John R. Ridpath, James A. Swenberg, Jun Nakamura. Genotoxicity of trace level of hexavalent chromium existing in city water. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5363. doi:10.1158/1538-7445.AM2014-5363