Imamura T, Gandy J, Hasegawa L
J Toxicol Environ Health. 1985;15(2):279-91. doi: 10.1080/15287398509530654.
O,O,S-Trimethyl phosphorothioate (OOS-Me) is a pneumotoxic impurity present in various organophosphorus insecticides. OOS-Me produces morphological alteration of bronchiolar epithelial Clara cells accompanied by an increase in pulmonary lavage lactate dehydrogenase activity and severe weight loss in rats. Tolerance to the pneumotoxicity of OOS-Me was induced rapidly by oral pretreatments with small doses of OOS-Me itself. O,O-Dimethyl-S-ethyl phosphorothioate (OOS-Et), a pneumotoxic trialkyl phosphorothioate that is closely related in structure to OOS-Me, also produced a tolerance by oral pretreatment with small doses of OOS-Et itself. Pretreatment of rats with OOS-Me produced tolerance to OOS-Et, pretreatment did not produce tolerance to OOS-Me. Pretreatment of rats with tolerance-inducing doses of OOS-Me or OOS-Et had no effect on pulmonary or hepatic monooxygenase activities. Malathion and phenthoate carboxylesterases in pulmonary and hepatic microsomes were inhibited by these pretreatments. Activity of superoxide dismutase in lung or glutathione content in lung or liver was not affected by these pretreatments. Although the mechanism(s) remains unknown, the present study demonstrated the tolerance development to the chemical-induced pneumotoxicity.
硫代磷酸O,O,S-三甲基酯（OOS-Me）是多种有机磷杀虫剂中存在的一种肺毒性杂质。OOS-Me会导致细支气管上皮克拉拉细胞发生形态改变，同时大鼠肺灌洗乳酸脱氢酶活性增加且体重严重减轻。通过口服小剂量的OOS-Me本身进行预处理可迅速诱导对OOS-Me肺毒性的耐受性。硫代磷酸O,O-二甲基-S-乙酯（OOS-Et）是一种与OOS-Me结构密切相关的肺毒性三烷基硫代磷酸酯，通过口服小剂量的OOS-Et本身进行预处理也可产生耐受性。用OOS-Me对大鼠进行预处理可产生对OOS-Et的耐受性，但预处理对OOS-Me本身不产生耐受性。用诱导耐受性剂量的OOS-Me或OOS-Et对大鼠进行预处理对肺或肝单加氧酶活性没有影响。这些预处理会抑制肺和肝微粒体中的马拉硫磷和稻丰散羧酸酯酶。这些预处理对肺中超氧化物歧化酶的活性或肺或肝中谷胱甘肽的含量没有影响。尽管其机制尚不清楚，但本研究证明了对化学诱导的肺毒性产生耐受性。
