Mutagenic effects of 3-carbethoxypsoralen and 8-methoxypsoralen plus 365-nm irradiation in mammalian cells.
Cell survival, i.e. colony-forming ability, and the induction of 6-thioguanine-resistant (6-TGr) mutants were determined in Chinese hamster V79 cells by using two photoreactive furocoumarins of photochemotherapeutic interest: the bifunctional compound 8-methoxypsoralen (8-MOP) and the monofunctional compound 3-carbethoxypsoralen (3-CPs). To quantify the mutation induction in V79 cells mutants deficient in the enzyme hypoxanthine-guanine phosphoribosyl transferase (HGPRT) were selected with the purine analogue 6-thioguanine (6-TG). The effects of the compounds alone at 50 microM in the absence of light and those of 365-nm radiation (UVA) at doses of up to 6 kJm-2 were negligible. When exposed to equimolar concentrations of the compounds together with UVA, V79 cells were about 8 times more sensitive to 8-MOP-plus-UVA than to 3-CPs-plus-UVA. Per unit dose of UVA, 8-MOP was about 7 times more effective than 3-CPs for the induction of 6-TGr mutants. The induction followed about one-hit kinetics for 3-CPs and about two-hit kinetics for 8-MOP. At 50% survival the frequency of 6-TGr mutants induced by 8-MOP plus UVA and 3-CPs plus UVA differed by a factor of about 3.5. These results show a marked concordance with those obtained in the yeast Saccharomyces cerevisiae: both compound exhibited lethal and mutagenic activities but the monofunctional compound 3-CPs was less lethal and mutagenic than the bifunctional compound 8-MOP.
D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006224:Cricetinae; D003412:Cricetulus; D004351:Drug Resistance; D011564:Furocoumarins / Q000633:toxicity*; D007041:Hypoxanthine Phosphoribosyltransferase / Q000172:deficiency; D007700:Kinetics; D008168:Lung; D008730:Methoxsalen / Q000633:toxicity*; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D013866:Thioguanine / Q000633:toxicity; D014466:Ultraviolet Rays
D011564:Furocoumarins; D009153:Mutagens; C017104:3-carbethoxypsoralen; D007041:Hypoxanthine Phosphoribosyltransferase; D013866:Thioguanine; D008730:Methoxsalen