GENOTOXIC EFFECTS OF STRUCTURALLY RELATED BETA-CARBOLINE ALKALOIDS

beta-Carboline alkaloids, found in medicinal plants, tobacco smoke and well-cooked foods, have shown a variety of actions in biological syst ems related to their interaction with DNA, Therefore, these alkaloids can be considered potentially mutagenic. In this work, the genotoxic, mutagenic, and cytotoxic activities of three aromatic beta-carboline a lkaloids (harman, harmine, and harmol) and two dihydro-beta-carboline alkaloids (harmaline and harmalol) were evaluated by means of the Salm onella/microsome assay (Salmonella typhimurium TA98, TA97, TA100, and TA102) and SOS chromotest (Escherichia coli PQ37) with and without met abolic activation. Moreover, harman and harmine were analyzed by the m icronucleus assay in vivo. It was shown that genotoxicity was inhibite d by the addition of S9 mix for aromatic beta-carbolines harman and ha rmol in TA97. However, harmine showed signs of mutagenicity only in th e presence of S9 mix in TA98 and TA97 frameshift strains. In the SOS c hromotest, only harman induced SOS functions in the absence of S9 mix. Dihydro-beta-carbolines were not genotoxic in any of the microorganis ms used, The negative responses obtained in the micronucleus assay ind icated that harman and harmine were not able to induce chromosomal mut ations. (C) 1997 Elsevier Science B.V.