The induction of prophage expression in different Salmonella typhimurium strains by DNA cross-linking and monoadduct forming psoralens and longwave ultraviolet radiation.
The cytotoxicity, and ability to induce the expression of prophage in Salmonella typhimurium LT2 strains has been examined for 4 furocoumarins, 8-methoxypsoralen (8-MOP), 5-methoxypsoralen (5-MOP), 3-carbethoxypsoralen (3-CP), and 5-methylisopsoralen (5-MI) given with ultraviolet-A radiation (u.v.A). 8-MOP and 5-MOP have a linear tricyclic structure and possess two photoreactive sites, the 3,4 and 4',5' double bonds, enabling them to form both monoadducts and interstrand cross-links with DNA. The angular structure of 5-MI imposes steric constraints preventing it from forming interstrand cross-links with DNA although it possesses both of the photoreactive double bonds. The substituent group at position C-3 in 3-CP blocks the 3,4 reactive site and 3-CP is thus incapable of forming interstrand cross-links; 3-CP is reportedly, unlike the other three furocoumarins, non-carcinogenic in mice. 8-MOP, 5-MOP, and 5-MI were very cytotoxic to both the base-pair (TA1535) and frame-shift (TA1538) tester strains when given with u.v.A. Comparable amounts of 3-CP given with u.v.A were much less toxic. 8-MOP, 5-MOP, and 5-MI were potent inducers of prophage expression in both TA1535 and TA1538. 3-CP was a very poor inducer of prophage. The cytotoxicity and prophage inducing ability of 5-MI + u.v.A indicate that these actions are not necessarily restricted to the DNA crosslinking psoralens. The lower toxicity of 3-CP + u.v.A is not a simple function of the ability of 3-CP to form only monoadducts with DNA. The ability or inability to induce the expression of prophage in S. typhimurium may be a rapid and useful screen for the potential phototoxicity and carcinogenicity of novel psoralens.
D004269:DNA, Bacterial / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D011564:Furocoumarins / Q000494:pharmacology*; D012483:Salmonella Phages / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D013329:Structure-Activity Relationship; D014466:Ultraviolet Rays; D014775:Virus Activation / Q000187:drug effects / Q000528:radiation effects*
D004269:DNA, Bacterial; D004279:DNA, Viral; D011564:Furocoumarins