Xiang Y Y, Wang D Y, Tanaka M, Igarashi H, Kamo T, Shen Q, Sugimura H, Kino I
First Department of Pathology, Hamamatsu University School of Medicine, Japan.
Pathol Int. 1995 Jun;45(6):415-21. doi: 10.1111/j.1440-1827.1995.tb03478.x.
Cancers and precancerous lesions of the esophagus were efficiently induced in rats by the simulation of a clinico-epidemiological setting; that is, the administration of precursors of nitrosamine. Six week old non-inbred male Wistar rats were given 2g/kg bodyweight of sarcosine ethyl ester hydrochloride (SEEH) and concurrently 0.3g/kg bodyweight of sodium nitrite (NaNO2), precursors of N-nitrososarcosine ethyl ester (NSEE), in 2% sucrose as drinking water. Group 1 received the precursors twice a week for 6 weeks followed by 8 weeks observation, and group 2, once every 3 days for 7 weeks followed by 26 weeks observation. At the end of treatment, no tumor had developed in the esophagus of rats in group 1, but the [3H]-thymidine labeling indices in both basal and superficial layer cells were higher than in the control group. On subsequent observation, papillomas appeared in group 1 (33.3%), and carcinomas in group 2 (33.3%), within 4 weeks. The tumors induced in group 1 were mostly papillomas and rarely carcinomas. When the observation was prolonged in group 2, 100% of the animals had cancer in week 20. The pathological changes of the lesions paralleled the sequential development of human squamous cell carcinoma of the esophagus. Our system has the advantages in that papillomas and cancers can be induced in rats in a short time and the agents used are less toxic than preformed nitrosamines administered previously by gastric intubation. It would serve as a useful experimental tool to study premalignant lesions and cancers of the esophagus.
通过模拟临床流行病学环境，即给予亚硝胺前体，可在大鼠中有效诱发食管癌和癌前病变。给6周龄的非近交系雄性Wistar大鼠饮用含2%蔗糖的水，其中含有2g/kg体重的盐酸肌氨酸乙酯（SEEH），同时含有0.3g/kg体重的亚硝酸钠（NaNO2），这两种物质是N-亚硝基肌氨酸乙酯（NSEE）的前体。第1组每周接受两次前体，共6周，随后观察8周；第2组每3天接受一次，共7周，随后观察26周。治疗结束时，第1组大鼠食管未出现肿瘤，但基底层和表层细胞的[3H]-胸腺嘧啶核苷标记指数均高于对照组。在随后的观察中，第1组在4周内出现了乳头状瘤（33.3%），第2组出现了癌（33.3%）。第1组诱发的肿瘤大多为乳头状瘤，很少为癌。当第2组的观察期延长时，在第20周时100%的动物发生了癌症。病变的病理变化与人类食管鳞状细胞癌的连续发展过程相似。我们的系统具有以下优点：能在短时间内诱导大鼠发生乳头状瘤和癌症，且所用试剂的毒性低于先前通过胃管给予的预制亚硝胺。它将成为研究食管癌前病变和癌症的有用实验工具。
