PROPHAGE INDUCTION, MUTAGENESIS AND CELL SURVIVAL OF AMES' MUTAGEN TESTER STRAINS AFTER 8-METHOXYPSORALEN PLUS ULTRAVIOLET LIGHT-A |
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Authors: | Larry A Wheeler Michel DeMeo† Nicholas Lowe† |
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Institution: | *Pharmacy Service, Research Unit, Veterans Administration, Wadsworth VA Medical Center, Los Angeles, CA 90073, U.S.A.;†Department of Pharmacology and Dental Research Institute, University of California, Los Angeles, CA 90024, U.S.A.;‡Combined ULCA-WADSWORTH Dermatology Program |
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Abstract: | Abstract— The furocoumarin 8-methoxypsoralen (8-MOP) is not detected as a mutagen in the standard Ames test either in the presence or absence of S9-mix and/or ultraviolet light-A (320–400 nm). The Ames strains have recently been shown to harbor bacteriophages that are inducible by carcinogens and mutagens. Psoralen (8-MOP) plus UVA (PUVA) was found to be a potent prophage inducing treatment. Induction was observed in TA1535, TA1538, TA98, TA100, TA1978 and TA1975 with 0.1 μg/ml of 8-MOP and 2.5 kJ/m2 of UVA. PUVA is a potent bactericidal treatment at concentrations of 8-MOP above 0.5 μg/ml and 2.5 kJ/m2 in tester strains TA1535, TA1538, TA98, and TA100. PUVA is known to be bactericidal, but the cytotoxicity observed in this study was unique in that the frameshift tester strains (TA1538 and TA98) were more sensitive to the lethal effects of PUVA than the base pair tester strains (TA1535 and TA100). The differential cytotoxicity in such closely related strains led to the examination of some of the strains from which the Ames strains were derived. The data suggest mutations introduced into the Ames strains to make them more sensitive to carcinogens and mutagens (Λ uvrB ) have resulted in an altered response to PUVA. It is postulated that TA1535 retains a DNA repair function that is lost by TA1538 during the selection for uvrB deficient strains. PUVA is also unique in that plasmid pKM101 does not confer enhanced survival of TA100 compared to TA1535 in contrast to many other carcinogens and mutagens. In conclusion, these data show that PUVA induces a pathway leading to prophage induction and demonstrates the potential use of prophage induction assays to detect mutagens and carcinogens that may otherwise be lethal to the Ames tester strains. |
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