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 ind uced in rats by the simulation of a clinicoepidemiological setting; th at is, the administration of precursors of nitrosamine. Six week old n on-inbred male Wistar rats were given 2g/kg bodyweight of sarcosine et hyl 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 precursor s 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 [H-3]-thymidine labeling indices in both basal and superficial layer cells were higher than in the control group. On sub sequent observation, papillomas appeared in group 1 (33.3%), and carci nomas in group 2 (33.3%), within 4 weeks. The tumors induced in group 1 were mostly papillomas and rarely carcinomas. When the observation w as prolonged in group 2, 100% of the animals had cancer in week 20. Th e pathological changes of the lesions paralleled the sequential develo pment of human squamous cell carcinoma of the esophagus. Our system ha s 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 nit rosamines administered previously by gastric intubation. It would serv e as a useful experimental tool to study premalignant lesions and canc ers of the esophagus.