DIAMINOTOLUENES INDUCE INTRACHROMOSOMAL RECOMBINATION AND FREE-RADICALS IN SACCHAROMYCES-CEREVISIAE

The carcinogenicity of aniline-based aromatic amines is poorly reflect ed by their activity in short-term mutagenicity assays such as the Sal monella typhimurium reverse mutation (Ames) assay. More information ab out the mechanism of action of such carcinogens is needed. Here we rep ort the effects on DEL recombination in Saccharomyces cerevisiae of th e carcinogen 2,4-diaminotoluene and its structural isomer 2,6-diaminot oluene, which is reported to be non-carcinogenic. Both compounds are d etected as equally mutagenic in the Salmonella assay. In the absence o f any external metabolizing system both compounds were recombinagenic in the DEL assay, with the carcinogen being a more potent inducer of d eletions than the non-carcinogen. In the presence of Aroclor-induced r at liver S9, however, the carcinogen 2,4-diaminotoluene became a 2-fol d more potent inducer of deletions, and the non-carcinogen 2,6-diamino toluene was rendered less toxic and no induced recombination was obser ved. 2,4-Diaminotoluene is distinguished from its non-carcinogen analo g in the DEL assay, therefore, on the basis of a preferential activati on of the carcinogen in the presence of a rat liver microsomal metabol izing system. Free radical species are produced by several carcinogens and have been implicated in carcinogenesis. We further investigated w hether exposure of yeast to either 2,4-diaminotoluene or 2,6-diaminoto luene resulted in a rise in intracellular free radical species. The ef fects of the free radical scavenger N-acetylcysteine on toxicity and r ecombination induced by the two compounds and intracellular oxidation of the free radical-sensitive reporter compound dichlorofluorescin dia cetate were studied. Both 2,4- and 2,6-diaminotoluene produced free ra dical species in yeast, indicating that the reason for the differentia l activity of the compounds for induced deletions is not reflected in any difference in the production of foe radical species. (C) 1997 Else vier Science B.V.