GENOTOXIC ACTIVITY OF CHLORINATED BUTENOIC ACIDS IN SALMONELLA-TYPHIMURIUM STRAINS TA98, TA100 AND TA104

The mutagenic activities of several chlorinated butenoic acids, recent ly identified in chlorinated drinking waters, were determined by the S almonella microsome assay. The Salmonella typhimurium tester strains T A98, TA100, and TA104 were used without S9 mix. The results from the i nvestigation showed that (Z)-2-chloro-3-(dichloromethyl)-4-oxobutenoic acid (MX, in the open form) was the most potent mutagen of the compou nds tested. However, a significant number of mutations was also induce d by compounds with structural similarities to MX. In general, all the compounds, except the butenedioic acids, were mutagenic in the assays for both base-pair substitution strains (TA100, TA104) and for the fr ameshift strain TA98, with the highest mutagenic response observed in strain TA100. When the aldehyde group of MX and of 2-chloro-3-(chloror nethyl)-4-oxobutenoic acid (CMCF, in the open form) was replaced by a dichloromethyl group, the mutagenic response in strains TA98 and TA104 changed. We concluded that a frame-shift mutation occurred because of the replacement. The increase of the TA104 mutagenicity suggested tha t adenosine could be the target for these types of compounds. Further evidence for such possibility were the modified adenosine adducts we c ould identify for some chlorinated butenoic acids. (C) 1998 Elsevier S cience B.V. All rights reserved.