Perera M I, Kunz H W, Gill T J, Shinozuka H
Transplantation. 1986 Sep;42(3):297-302. doi: 10.1097/00007890-198609000-00014.
Dietary administration of cyclosporine (CsA) to rats induces lymphoproliferative disorders involving the gut lymphoid plaques with frequent mucosal ulceration. In this study, we investigated whether administration of a known chemical carcinogen prior to CsA treatment modifies the development of the lesions induced by CsA. Male Sprague-Dawley rats were given either a single i.p. injection of N-methyl N-nitrosourea (MNU) (25 mg/kg) or the solvent--and one week thereafter they were fed a diet containing 0.011% CsA. Control rats were fed a basal diet with or without prior MNU treatment. Of the rats that received MNU and CsA, 60% developed adenocarcinomas of the small and large intestine arising in the regions of the intestinal lymphoid plaques. Only 1 of 12 rats given MNU followed by a basal diet developed adenocarcinoma. No tumors developed in rats treated with CsA alone, but there was atypical proliferation of the intestinal mucosa in conjunction with lymphoid hyperplasia of the gut. The mucosal damage secondary to CsA-induced lymphoid lesions probably acted as a promoting stimulus for the development of intestinal carcinomas.
给大鼠喂食环孢素（CsA）会诱发淋巴增殖性疾病，累及肠道淋巴滤泡，并频繁出现黏膜溃疡。在本研究中，我们调查了在CsA治疗前给予已知化学致癌物是否会改变CsA诱导的病变发展。给雄性Sprague-Dawley大鼠单次腹腔注射N-甲基N-亚硝基脲（MNU）（25 mg/kg）或溶剂，一周后给它们喂食含0.011% CsA的饲料。对照大鼠喂食基础饲料，有无MNU预处理均可。接受MNU和CsA的大鼠中，60%在肠道淋巴滤泡区域发生了小肠和大肠腺癌。仅1只接受MNU后再喂食基础饲料的12只大鼠发生了腺癌。单独用CsA治疗的大鼠未发生肿瘤，但出现了肠黏膜非典型增生并伴有肠道淋巴组织增生。CsA诱导的淋巴病变继发的黏膜损伤可能对肠道癌的发展起到了促进作用。
