Mutagenic activity of three monofunctional and three bifunctional furocoumarins in yeast (Saccharomyces cerevisiae).

The mutagenic activity of photoadditions induced by 4,5'-dimethylangelicin (4,5'-DMA), 3-carbethoxypsoralen (3-CPs), angelicin, 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP) and 4,5',8-trimethylpsoralen (TMP), was studied in haploid yeast cells at the nuclear and cytoplasmic levels. With regard to the induction of cell killing 4,5'-DMA and 3-CPs were about 5 to 6 times more active than 8-MOP probably due to an efficient repair of 4,5'-DMA or 3'CPs induced monoadditions in DNA. 4,5'-DMA was about 5-fold less active than angelicin, reflecting the different photoreactivities of the compounds towards DNA. In accord with its monofunctional activity, 4,5'-DMA was less efficient on the induction of nuclear reversions but more efficient on the induction of cytoplasmic "petite" mutants per viable cell than 8-MOP and the other bifunctional compounds. In contrast to 3-CPs and angelicin, the reversion induction by 4,5'-DMA followed a 2 hit kinetics. For the induction of CanR forward mutants per viable cell 4,5'-DMA was more efficient than 3-CPs and approached the activity of 8-MOP; angelicin, 5-MOP and TMP were slightly more efficient than 8-MOP, whereas 3-CPs was clearly less efficient. Thus, the monofunctional furocoumarins exert different genotoxic effects when compared on a survival basis. Cell killing effects in the presence and in the absence of oxygen were also evaluated.