GENOTOXICITY INDUCED BY FUROCOUMARIN HYDROPEROXIDES IN MAMMALIAN-CELLS UPON UVA IRRADIATION

The mutagenicity and micronucleus induction by the furocoumarin hydrop eroxides 1a and 2a and, for comparison, their corresponding alcohols 1 b and 2b were investigated in L5178Y tk(+/-) mouse lymphoma cells and AS52 Chinese hamster ovary cells. The furocoumarin hydroperoxide 1a en hanced the micronucleus frequency in L5178Y tk(+/-) mouse lymphoma cel ls significantly, while its alcohol 1b exhibited a rather moderate eff ect. In contrast, both the furocoumarin hydroperoxide 2a and its alcoh ol 2b induced high frequencies of micronuclei. Only the furocoumarin h ydroperoxide 1a, but not its alcohol 1b, was mutagenic in both L5178Y tk(+/-) and AS52 cells. On the other hand, the furocoumarin hydroperox ide 2a and its alcohol 2b were mutagenic. For all furocoumarin derivat ives 1a,b and 2a,b no mutagenicity and genotoxicity was observed in th e absence of UVA light. The multifunctional furocoumarin hydroperoxide s may serve as potential photochemotherapeutic agents. (C) 1995 Academ ic Press, Inc.