Atypical hyperplasia of choledocho-pancreatic duct epithelium in an Otsuka Long Evans Tokushima Fatty strain of rats.

Epithelial papillary hyperplasia of choledocho-pancreatic duct, associated with cellular atypism, was observed in Otsuka Long Evans Tokushima Fatty (OLETF) rats, a strain originally established as an animal model for non-insulin-dependent diabetes mellitus (NIDDM). To investigate the potential feasibility of OLETF rats as an animal model for pancreatic ductal carcinoma, we examined the pathological characteristics of ductal lesions in OLETF rats aged from 5 to 50 weeks. Hyperplastic lesions in OLETF rats became apparent after 10 weeks of age and increased in severity and frequency of atypical changes in hyperplastic epithelium appearing after 20 weeks. We compared ductal lesions from OLETF rats with those from age-matched Long Evans Tokushima Otsuka (LETO) rats, which share a similar genetic background with OLETF rats but do not develop NIDDM. While LETO rats also display a tendency toward ductal hyperplasia, lesions from OLETF rats were more numerous and larger in size than those from age-matched LETO rats. In addition, lesions from OLETF rats contained a significantly higher number of proliferating cell nuclear antigen-positive cells than those from LETO rats. Finally, lesions in OLETF rats were accompanied by inflammation, and the observed morphological alteration of lesions correlated well with the grade of inflammation.