Photomutagenesis by chlorinated phenothiazine tranquilizers.
Photomutagenesis by chlorinated phenothiazine tranquilizers.
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氯化吩噻嗪镇静剂的光诱变。
DOI：
10.1073/pnas.76.1.469
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发表时间：
1979
影响因子：
11.1
通讯作者：
J. Jose
中科院分区：
文献类型：
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作者：
J. Jose
吩噻嗪镇静剂是广泛使用的药物，与副作用有关，如白内障的形成，似乎与光照有关。由于患者可能会在很长一段时间内使用它们，因此重要的是要确定这些药物可能引起的有害细胞效应，并且如果可能的话，选择或设计不会引起此类效应的药物。本文报道的结果表明，氯代吩噻嗪类药物可被光活化为致突变物质，而非氯代类似物则不具备这一特性。在黑暗中，检测的吩噻嗪均无致突变性。仅在缺乏DNA切除修复的鼠伤寒沙门氏菌菌株中观察到致突变性，并且在含有质粒pKM 101的菌株中致突变性升高，这可能增强易错修复。
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.