Comparative bacterial mutagenicity studies with 8-methoxypsoralen and 4,5',8-trimethylpsoralen in the presence of near-ultraviolet light and in the dark.
2 strains of S. typhimurium, TA98 and TA100, and 2 strains of E. coli, WP2(pKM101) and WP2uvrA-(pKM101) were used to study mutagenesis by 8-methoxypsoralen (8-MOP) and 4,5',8-trimethylpsoralen (4,5',8-TMP) in the dark and in the presence of near-ultraviolet (NUV) light both without metabolic activation and with rat-liver S9 at 3 levels (4, 10 and 30% in standard cofactors). The S9-independent base substitution mutagenic activity of 8-MOP plus NUV light was confirmed in WP2(pKM101), and a similar activity was seen for 4,5',8-TMP, although neither substance was active in TA100. The frameshift mutagenic activity of 8-MOP in the dark in TA98 was not confirmed despite histidine levels which would ensure DNA replication, but this may be due to the lower concentrations of 8-MOP achieved in the common solvent system adopted. Both 8-MOP and 4,5',8-TMP were mutagenic in WP2uvrA-(pKM101) after microsomal activation, and the responses were similar whether experiments were conducted in the dark or in NUV light. In view of the oral administration of 8-MOP to psoriasis patients, this finding may be of relevance in risk assessment, and tends to suggest that topical application of 4,5',8-TMP to psoriatic patients may present reduced risk of malignant disease.
D000818:Animals; D001711:Biotransformation; D003624:Darkness; D011564:Furocoumarins / Q000494:pharmacology*; D008730:Methoxsalen / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000378:metabolism; D009152:Mutagenicity Tests; D009153:Mutagens; D009154:Mutation; D051381:Rats; D012486:Salmonella typhimurium / Q000187:drug effects / Q000528:radiation effects; D013045:Species Specificity; D014307:Trioxsalen / Q000494:pharmacology*; D014466:Ultraviolet Rays
D011564:Furocoumarins; D009153:Mutagens; D008730:Methoxsalen; D014307:Trioxsalen