CHLOROFORM AND CARBON-TETRACHLORIDE INDUCE INTRACHROMOSOMAL RECOMBINATION AND OXIDATIVE FREE-RADICALS IN SACCHAROMYCES-CEREVISIAE

Chlorination of drinking water results in the generation of low levels of numerous chlorinated hydrocarbons due to the reaction of chlorine with naturally occurring organic compounds in the water. Concern has b een raised about the safety of these chlorinated contaminants as sever al of them, most notably chloroform (trichloromethane), have been show n to be carcinogenic in long-term rodent bioassays and weak correlatio ns between trihalomethane levels in drinking water and an increased ri sk of bladder and colorectal cancer in humans have been found. Chlorof orm and carbon tetrachloride induce liver cancer in rats and mice only at doses where significant hepatotoxicity is observed and have been c lassed as non-genotoxic carcinogens. We have investigated the ability of chloroform, carbon tetrachloride and 1,1,1-trichloroethane to induc e deletions via intrachromosomal recombination in the yeast Saccharomy ces cerevisiae. Chloroform and carbon tetrachloride induced this genot oxic recombination event at similar doses, 1,1,1-Trichloroethane gave only a weak response in the DEL recombination assay and only at the hi ghest dose. We further show that chloroform and carbon tetrachloride, but not trichloroethane, induced oxidative free radical species in our yeast strain. The free radical scavenger N-acetylcysteine reduced chl oroform-induced toxicity and recombination, and both chloroform and ca rbon tetrachloride were able to oxidize the free radical-sensitive rep orter compound dichlorofluorescein diacetate in vivo. The implications of these findings to the carcinogenic activities of the three compoun ds are discussed. (C) 1998 Elsevier Science B.V.