Lefevre P A, Ashby J
Environ Mutagen. 1985;7(6):833-7. doi: 10.1002/em.2860070605.
Cimetidine is widely prescribed as a palliative or cure for gastric disorders in man. It is known to be noncarcinogenic to rodents and has been shown to be inactive in a wide range of in vitro and in vivo genotoxicity assays. It was therefore of concern when an injectable formulation of this drug (Cimetex) was reported to initiate UDS in cultured primary rat hepatocytes [Martelli et al, 1983]. We have confirmed the ability of Cimetex to elicit UDS in primary hepatocytes and established that cimetidine itself is inactive. These data indicate that it is not cimetidine per se, but rather its protonated formulation which is responsible for the activity. These observations pose fundamental questions regarding the validity of the UDS end-point when testing salts in vitro, rather than presenting a challenge to the nongenotoxic status of cimetidine.
西咪替丁作为治疗人类胃部疾病的姑息性药物或治愈药物被广泛使用。已知它对啮齿动物无致癌性，并且在广泛的体外和体内遗传毒性试验中均显示无活性。因此，当有报道称这种药物的一种注射剂（西美泰）能在原代大鼠肝细胞培养物中引发未修复的DNA合成（UDS）时，人们对此表示关注[马尔泰利等人，1983年]。我们已经证实西美泰能在原代肝细胞中引发UDS，并确定西咪替丁本身无活性。这些数据表明，具有活性的不是西咪替丁本身，而是其质子化形式。这些观察结果提出了关于在体外测试盐类时UDS终点有效性的基本问题，而不是对西咪替丁的非遗传毒性状态构成挑战。
