硒抗砷、氟、甲基汞致畸作用的体外实验研究

AN EXPERIMENTAL STUDY ON SELENIUM ANTAGONISM OF ARSENIC,FLUORIDE AND MENTHYLMERCURY INDUCED TERATOGENESIS IN VITRO

用大鼠全胚胎培养法并结合电镜技术探讨了硒与砷、氟、甲基汞之间是否存在交互作用及作用类型。结果表明三者均能诱发体外培养的胚胎发育异常，并呈剂量反应关系。加入０．５μｇ／ｍｌ硒后明显拮抗１．０μｇ／ｍｌ砷、１０μｇ／ｍｌ氟和０．４μｇ／ｍｌ汞的致畸性及胚胎毒性，但不能缓解３．０μｇ／ｍｌ砷和２０μｇ／ｍｌ氟的发育毒性，主要呈现砷、氟的独立作用。脏层卵黄囊（ＶＹＳ）是硒抗砷、氟致畸效应的主要位点之一，１．０μｇ／ｍｌ砷和１０μｇ／ｍｌ氟所导致ＶＹＳ超微结构的病理改变在相应联合组均消失。然而，汞和硒＋汞对ＶＹＳ结构无明显的损害作用，说明≤０．４μｇ／ｍｌ汞能迅速通过ＶＹＳ而直接攻击胚胎细胞。结果提示，ＶＹＳ结构与功能紊乱是砷、氟致畸的重要机制之一，也与硒、砷、氟之间拮抗作用的机制有关。

Whole embryo culture technique and electron microscopy were used to study interaction of arsenic,fluoride and mentylmercury with selenium in vitro during early organogenesis of rat embryos.Results showed arsenic,fluoride and menthylmercury could induce death,malformation and retardation in embryonic growth and development in vitro,with an apparent dose-effect relationship.After the addition of 0.5 μg/ml selenium,the teratogenicity and embryotoxicity of 1.0μg/ml arsenic,10μg/ml fluoride and 0.4μg/ml menthylmercury were significantly antagonized.However,because selenium could not ameliorate developmental toxicity of 3.0μg/ml arsenic and 20μg/ml fluoride,the results were independent effect of arsenic or fluoried.Visceral yolk sac(VYS) was an important 'target' site of selenium antagonism of arsenic or fluoride induced teratogenesis in vitro.All pathological changes of VYS induced by 1.0μg/ml arsenic and 10μg/ml fluoride have disappered with selenium added in rat serum cluture in vitro.Menthylmercury didn't damage ultrastructures of VYS with or without selenium.It is evident that menthylmercury can quickly pass through VYS and directly attack embryos.The results suggest that:1)disorders of VYS structure and function were one of teratogenic mechanisms of arsenic or fluoride and 2) would be related to mechanism of interaction between selenium and arsenic or fluoride.