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MUTAGENICITY IN SALMONELLA AND DNA DAMAGE IN THE CHO/COMET ASSAY INDUCED BY NITROHALOMETHANES, A NOVEL CLASS OF DRINKING WATER DISINFECTION BY-PRODUCTS
Citation:
Kundu, B., S. H. Warren, D M. DeMarini, S D. Richardson, E. D. Wagner, AND M. J. Plewa. MUTAGENICITY IN SALMONELLA AND DNA DAMAGE IN THE CHO/COMET ASSAY INDUCED BY NITROHALOMETHANES, A NOVEL CLASS OF DRINKING WATER DISINFECTION BY-PRODUCTS. Presented at Environmental Mutagen Society Mtg, San Diego, California, March 16-21, 2001.
Description:
Mutagenicity in Salmonella and DNA Damage in the CHO/Comet Assay Induced by Nitrohalomethanes, a Novel Class of Drinking Water Disinfection By-Products.
Halomethanes are a class of drinking water disinfection by-products (DBPs) whose genotoxicity has been studied extensively, with most halomethanes inducing mutagenic, clastogenic, and carcinogenic effects. Recently, a related class of DBPs, nitrohalomethanes (NHMs), has been identified in drinking water. These NHMs are predicted to have potential adverse health effects and are currently part of a nationwide occurrence study of DBPs in drinking water. Although they have been predicted to be toxic, no genotoxicity data had yet been generated for these compounds. NHMs are similar in chemical structure to well-studied halomethanes, with the addition ofa nitro-group (NO2). We examined the mutagenicity of NHMs in Salmonella strains TA98, TA1OO, TA1O4, and RSJ1OO and their DNA damaging ability in a single-cell gel electrophoresis (Comet) assay with Chinese hamster ovary (CHO) cells. The NHMs induced revertants in all Salmonella strains, about three-fold above background levels. In the Comet
assay? these DBPs showed a DNA-damaging capability of over one order of magnitude above
the drinking water contaminant Mx, a potent genotoxicant. Though there is agreement with the qualitative results from the two systems, the potency of the NHMs differs in each system. In Salmonella, NHMs were generally weak mutagens and not as potent as their analogous halomethanes (minus the NO2 group). The addition of a nitro-group to the halomethanes reduces the base-substitution mutagenicity of the NHMs. The NHMs were potent inducers of DNA damage in mammalian cells and may reflect high risk to humans. Future research will be focused on analyzing Salmonella revertants induced by NHMs using colony probe hybridization and PCR/DNA sequence analysis.
Abstract does not necessarily represent the policy of the US EPA.