Mutagenic effects photoinduced in normal human lymphoblasts by a monofunctional pyridopsoralen in comparison to 8-methoxypsoralen.
The photobiological effects induced by the monofuctional 7-methylpyrido[3,4-c]psoralen (MePyPs) in comparison to the bifunctional furocoumarin 8-methoxypsoralen (8-MOP) have been studied in a human lymphoblast cell line TK6. We report that, in human lymphoblasts, the cytotoxic effect of MePyPs plus UVA (365 nm) is much higher than that of 8-MOP plus 365-nm irradiation. The dose-modifying factor at the 37% survival level between the 2 compounds equals 120. Mutation induction by photoactivated MePyPs and 8-MOP has been studied in 2 genetic loci, hypoxanthine phosphoribosyl transferase (HPRT) and Na+/K+ ATPase. For equal UVA doses, the mutagenic effectiveness of MePyPs was higher than that of 8-MOP. However at equal survival levels, the mononfuctional psoralen MePyPs was less efficient than the bifunctional 8-MOP. In other words, compared to 8-MOP, the monofunctional agent MePyPs is more cytotoxic than mutagenic. This higher phototoxic and mutagenic efficiency of MePyPs in comparison to 8-MOP is likely to be related to the chemical nature of MePyPs-induced lesions which may be responsible for a reduced recognition and/or accessibility of the repair enzymes to damaged DNA.
Papadopoulo
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Institut Curie, Section de Biologie, URA 1292, CNRS, Paris, France.
Moustacchi
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D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006224:Cricetinae; D004249:DNA Damage; D004351:Drug Resistance / Q000235:genetics; D011564:Furocoumarins / Q000633:toxicity*; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D008730:Methoxsalen / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens; D010042:Ouabain / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics; D013866:Thioguanine / Q000494:pharmacology; D014466:Ultraviolet Rays
D011564:Furocoumarins; D009153:Mutagens; D010042:Ouabain; C044264:pyrido(3,4-c)-7-methylpsoralen; D007041:Hypoxanthine Phosphoribosyltransferase; D000254:Sodium-Potassium-Exchanging ATPase; D013866:Thioguanine; D008730:Methoxsalen