Genotoxicity of the isoquinoline alkaloid berberine in prokaryotic and eukaryotic organisms.

Berberine, a medically important isoquinoline alkaloid, was tested for the presence of genotoxic, mutagenic and recombinogenic activities in microorganisms. This alkaloid did not show genotoxic activity with or without metabolic activation in the SOS chromotest. It was also unable to induce significant cytotoxic, mutagenic or recombinogenic effects during treatments performed under nongrowth conditions. However, in dividing cells, this alkaloid induced important cytotoxic and cytostatic effects in proficient and repair-deficient Saccharomyces cerevisiae strains. Among the different repair-deficient mutants examined, a mutant blocked in the DNA strand-break repair pathway (rad52-1) was found to be the most sensitive to the cytotoxic effect of berberine. A triple mutant blocked in the excision (rad2-6), in the mutagenic (rad6-1) and in the recombinogenic (rad52-1) repair pathways demonstrated the same sensitivity as the single rad52-1 mutant. In dividing cells, the induction of frameshift and mitochondrial mutations, as well as crossing over, showed that this alkaloid is not a potent mutagenic agent. The possible implication of DNA topoisomerases in berberine toxicity mechanisms is discussed.