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IS GENOTOXICITY A POTENTIAL MODE OF ACTION FOR THE CARCINOGENICITY OF BROMATE
Citation:
Brock, K H., D D. Collard, AND R M. Zucker. IS GENOTOXICITY A POTENTIAL MODE OF ACTION FOR THE CARCINOGENICITY OF BROMATE. Presented at GEMS Meeting, Research Triangle Park, NC, October 25, 1999.
Description:
The EPA Office of Drinking Water is currently performing a risk assessment analysis of bromate, an ozonation disinfection by-product. Possible exposure to chlorination disinfection by-products in finished drinking water has heightened concern for public health safety. As a consequence, many utilities are using ozonation as an alternative treatment method. However, very little is known about the health risk associated with the disinfectant by-products of ozonation. The occurrence of bromate in ozonated drinking water ranges from 5-100 ug/L, in areas of the U.S. where source waters contain enhanced levels of bromide. Potassium bromate is a reported rat (kidney, mesotheliurn, thyroid) and mouse (kidney) carcinogen. We have evaluated the mutagenic potential of potassium bromate (CAS # 7758-01-2) and sodium bromate (CAS # 7789-38-0), both ozonation disinfection by-products, at the Tk locus of mouse lymphoma cells. To gain additional information on bromate, we have measured the capability of potassium bromate to induce apoptosis and specific cell cycle perturbations using flow cytometry.
Both sodium and potassium bromate demonstrated a positive mutagenic dose response and were active within the same concentration range (660-2653 ?M). The lowest effective concentration (660 ?M) was the same for both compounds and occurred with minimal cytotoxicity (Survival 70-80%). A significant induction of small colony mutants was observed indicative of a clastogenic mode of action for bromate. Flow cytometric analysis was performed on DNA samples stained with propidium iodide 2 h post-treatment. A dose dependent increase of G2/M cells was observed. Few cells with a DNA content lower than that of G1 cells (i.e. apoptotic cells) were present. The most conspicuous cell cycle perturbation observed 2 h post-treatment was a mid-S block. These results indicate that apoptosis is not present 2 h post-treatment, but normal cell-cycle kinetics is interrupted. The positive mutagenic response observed indicates that bromate has the potential to induce tumors by a genotoxic mode of action.