Photopromotion of sister chromatid exchanges by psoralen derivatives.
Several derivatives of 8-methoxypsoralen and 4,5'8-trimethylpsoralen were compared with respect to their photopromotion of sister chromatid exchanges. Peripheral blood leukocytes from heparinized blood of human volunteers were cultivated for 24 h. Selected flasks received psoralens (6.5 X 10(-8) M) and/or were irradiated (UV-A, 365 nm, 0.9 J/cm2). Bromodeoxyuridine (20 micrograms/ml) was added and flasks were further incubated for 48 h when colchicine was added. Spreads of mitotic chromosomes were prepared, stained with Hoechst 33258 and Giemsa, and scored for the number of sister chromatid exchanges (SCEs) per 100 chromosomes. Results were: Control (16.5); 8-methoxypsoralen (23.9); 5'-methyl-8-methoxypsoralen (25.7); 4-methyl-8-methoxypsoralen (27.8); 4,5'-dimethyl-8-methoxypsoralen (31.9); 4'-methoxymethyl, 4,5'8-trimethylpsoralen (42.9); 4'aminomethyl, 4,5'8-trimethylpsoralen-hydrochloride (59.1); 4'hydroxymethyl,4,5'8-trimethylpsoralen (75). In general, the psoralens with strong affinity for DNA as determined by KD values promoted more SCEs than did those with lower affinity. Trimethylpsoralen and its derivatives promoted more SCEs than did 8-methoxypsoralen and its derivatives, which may be indicative of relative DNA cross-linking potential.
D002478:Cells, Cultured; D003434:Crossing Over, Genetic / Q000187:drug effects*; D004247:DNA / Q000378:metabolism; D011564:Furocoumarins / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D007962:Leukocytes / Q000648:ultrastructure; D012854:Sister Chromatid Exchange / Q000187:drug effects* / Q000528:radiation effects; D012995:Solubility; D014466:Ultraviolet Rays
D011564:Furocoumarins; D004247:DNA