DEVELOPMENT OF A MODEL OF PANCREATIC CARCINOGENESIS - PROMOTING AND PROGRESSING EFFECTS OF TOTAL-BODY GAMMA-IRRADIATION ON PANCREAS OF NITROSOMETHYLUREA-TREATED RATS

Previous studies carried out by the same Authors have shown that a sin gle intraperitoneal injection of nitrosomethylurea (NMU) at day 3 of a ge induces in Wistar rat pancreas multicentric focal acinar cell hyper plasia (FACH). In this investigation a number of NMU-treated rats and saline (SAL)-injected rats, were exposed at day 30 of age to a single dose of whole body gamma irradiation (I, 400 or 600 cgy). The remainin g (NMU or SAL injected rats) received no irradiation (NI). Experimenta l groups: NMU-I (400 and 600 cgy); SAL-I (499 and 600 gy); NMU-NI and SAL-NI. Pancreas of NMU-I group rats contained FACH, dysplastic focy ( DYF) and carcinomas in situ (CIS) suggesting promoting and progressing effects of gamma radiation on NMU-treated rats. The incidence of CIS was dose-dependent. In SAL-I groups there was increased diffuse cell p roliferation, which was dose-dependent. Mitotic and apoptotic cells we re increased in number following irradiation. A two-stage protocol of pancreatic carcinogenesis consisting of NMU initiation and gamma radia tion promotion was developed.