Association of long lasting unsurmountable histamine H2 blockade and gastric carcinoid tumours in the rat.
Association of long lasting unsurmountable histamine H2 blockade and gastric carcinoid tumours in the rat.
复制标题
长期难以克服的组胺 H2 阻断与大鼠胃类癌之间的关联。
作者：
D. Poynter;C. R. Pick;R. Harcourt;S. Selway;G. Ainge;I. Harman;N. Spurling;P. Fluck;J. L. Cook
给总共 378 只大鼠口服洛西丁（一种有效的组胺 H2 拮抗剂），剂量为 50、185 或 685 mg/kg/天，持续 116 周，结果导致胃底类癌瘤的晚期形成。第一个这样的肿瘤是在治疗 712 天后被发现的。没有与剂量相关的反应；低处理水平的11只大鼠受到影响，中处理水平的12只大鼠受到影响，高处理水平的11只大鼠受到影响。二十七名女性受到影响，但只有七名男性受到影响。 228 名对照者中未发现胃肿瘤。没有证据表明洛西替丁是直接致癌物，有人认为肿瘤是由一种强效且难以克服的组胺 H2 受体拮抗剂引起的长期胃酸缺乏造成的。
The oral administration of loxtidine, a potent histamine H2-antagonist, to a total of 378 rats at doses of 50, 185, or 685 mg/kg/day for 116 weeks resulted in the late formation of carcinoid tumours of the gastric fundus. The first such tumour was detected after 712 days of treatment. There was no dose related response; 11 rats at the low level of treatment were affected, 12 at the intermediate and 11 at the high. Twenty seven females but only seven males were affected. No gastric tumours were found in the 228 controls. There is no evidence that loxtidine acts as a direct carcinogen and it is suggested that the tumours were the result of prolonged achlorhydria produced by a potent unsurmountable histamine H2 receptor antagonist.