Jose J G
Proc Natl Acad Sci U S A. 1979 Jan;76(1):469-72. doi: 10.1073/pnas.76.1.469.
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.
吩噻嗪类镇静剂是广泛使用的药物，它们会产生一些副作用，比如形成白内障，而这些副作用似乎与光照有关。由于患者可能长时间使用这些药物，因此确定这些药物可能会导致哪些有害的细胞效应，并在可能的情况下选择或设计不会产生此类效应的药物就显得很重要。此处报告的结果表明，氯化吩噻嗪类药物可被光激活成为诱变剂，而非氯化类似物则不具备这一特性。所测试的吩噻嗪类药物在黑暗中均无诱变性。仅在缺乏DNA切除修复功能的鼠伤寒沙门氏菌菌株中观察到诱变性，并且在含有质粒pKM101的菌株中诱变性增强，该质粒可能会增强易错修复。
