Mutagenicity and toxicity of furocoumarins: comparative investigations in 2 test systems.
The phototoxicity and the photomutagenicity of the 2 linear furocoumarins 8-methoxypsoralen (8-MOP) and 8-isoamylenoxypsoralen (8-IOP) and of the angular derivative 5'-methylangelicin (5'-MA) were studied in 2 different test systems. In human lymphocytes, sister-chromatid exchange analysis (SCE analysis) was carried out. We found an increase in SCE frequency after treatment with 8-MOP and 5'-MA, but no enhancement was caused by 8-IOP. In the algal system Chlamydomonas reinhardii, 8-MOP and 5'-MA showed a similarly strong influence with regard to phototoxicity; 8-IOP exhibited a weaker effect within the same irradiation time. For photomutagenicity in Chlamydomonas, 8-MOP proved to be the strongest derivative; 8-IOP, however, was capable of inducing about the same numbers of revertants, but only under certain conditions. The angular 5'-MA showed a weak mutagenic activity in contrast to the psoralens. The influence of the structure of the derivatives and of the experimental conditions on the effects obtained are discussed with regard to the therapeutic risk of monofunctional and bifunctional furocoumarins.
D002478:Cells, Cultured; D002696:Chlamydomonas / Q000187:drug effects* / Q000528:radiation effects; D003434:Crossing Over, Genetic / Q000187:drug effects*; D011564:Furocoumarins / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000502:physiology; D008730:Methoxsalen / Q000494:pharmacology*; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D012854:Sister Chromatid Exchange / Q000187:drug effects*; D014466:Ultraviolet Rays
D011564:Furocoumarins; D009153:Mutagens; C023026:5-methylangelicin; C031534:imperatorin; D008730:Methoxsalen