Genotoxic and recombinogenic activities of the two beta-carboline alkaloids harman and harmine in Saccharomyces cerevisiae.

The cytotoxical beta-carboline alkaloids harman and harmine occur in medical plants and in a variety of foods, alcoholic beverages, and industrial waste. We applied them to the yeast Saccharomyces cerevisiae to test for putative genotoxicity, mutagenicity and recombinogenicity and to determine whether harman and harmine produced repairable DNA damage. Harmine was more cytotoxic than harman for exponentially growing haploid and diploid cells. Only harmine-induced crossing-over and mitotic gene conversion but both alkaloids were frameshift mutagens in yeast. Mutants defective in excision-resynthesis repair (rad3 and rad1), in error-prone repair (rad6) and in recombinational repair (rad52) showed enhanced sensitivity to harmine and harman, but the ranking of sensitivities was different for the two alkaloids. It appears that both alkaloids are probably capable of inducing DNA single and/or double strand breaks. An epistatic interaction was shown between rad3-e5 and rad52-1 mutants alleles, indicating that excision-resynthesis and strand-break repair may have common steps in the repair of DNA damage induced by these alkaloids. The non-epistatic interaction observed in rad1Delta rad6Delta double mutants indicated that both excision-resynthesis and error-prone repair are independently involved in repair of harman- and harmine-induced DNA lesions.