Genetic effects of DNA mono- and diadducts photoinduced by furocoumarins in eukaryotic cells.
The genotoxic activity of two bifunctional furocoumarins, 8- and 5-methoxypsoralen (8-MOP and 5-MOP), and the newly developed monofunctional furocoumarin, 7-methyl-pyrido(3,4-c)psoralen (MePyPs), was determined in diploid yeast. In parallel experiments, the DNA photobinding capacity of the compounds was estimated. This capacity was, in decreasing order, MePyPs greater than 5-MOP greater than 8-MOP. The lesions induced by 8- and 5-MOP, which consist of a mixture of mono- and diadducts, were found to be more genotoxic than the monoadducts induced by MePyPs. A difference in specificity of MePyPs-induced lesions was observed for the induction of mutations and mitotic gene conversion. In Chinese hamster V79 cells, 5-MOP showed a higher DNA photobinding activity than 8-MOP. In spite of this, 5-MOP-induced lesions were less genotoxic, on a one-to-one basis, than those induced by 8-MOP. An analysis of the DNA cross-linking capacity of the two furocoumarins in V79 cells by alkaline elution suggests that, at a given dose of 365-nm radiation, 5-MOP produces more photoadducts than 8-MOP but the same number of DNA cross-links, and the ratio of mono- to diadducts induced is higher for samples treated with 5-MOP than for those treated with 8-MOP. This may offer an explanation for differences observed in the mutagenic and carcinogenic activity of these compounds.
D000078223:5-Methoxypsoralen; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D003432:Cross-Linking Reagents; D004247:DNA / Q000187:drug effects*; D011564:Furocoumarins / Q000633:toxicity; D005785:Gene Conversion / Q000187:drug effects; D008730:Methoxsalen / Q000633:toxicity*; D009154:Mutation / Q000187:drug effects; D010777:Photochemistry; D011995:Recombination, Genetic / Q000187:drug effects; D012441:Saccharomyces cerevisiae / Q000187:drug effects; D014466:Ultraviolet Rays
D003432:Cross-Linking Reagents; D011564:Furocoumarins; D000078223:5-Methoxypsoralen; C044264:pyrido(3,4-c)-7-methylpsoralen; D004247:DNA; D008730:Methoxsalen