Efficient and specific induction of esophageal tumors in rats by precursors of N-nitrososarcosine ethyl ester.

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.