Photomutagenesis by chlorinated phenothiazine tranquilizers

Phenothiazine tranquilizers are widely used pharmaceuticals that have been associated with side effects, such as formation of cataracts, that seem related to light exposure. Because patients may use them over extensive time periods, it is important to determine what deleterious cellular effects these drugs may cause and, if possible, to select or design drugs that do not cause such effects. The results reported here demonstrate that chlorinated phenothiazine drugs can be photoactivated to mutagenic species, whereas the nonchlorinated analogues do not possess this characteristic. None of the phenothiazines tested is mutagenic in the dark. Mutagenicity was observed only in strains of Salmonella typhimurium that lacked excision repair of DNA, and the mutagenicity was elevated in strains that contained the plasmid pKM101, which may enhance error-prone repair.