Characterization of a 4-month protocol for the quantitation of BOP-induced lesions in hamster pancreas and its application in studying the effect of dietary fat

Abstract

The early putative pre-neoplastic lesions which arise in the Syrian golden hamster pancreas prior to the appearance of carcinomas following treatment with N-nitrosobis(2-oxopropyl)amine (BOP), have been characterized and quantitated in order to refine a protocol which permits post-initiation modulation to be evaluated within a relatively short period of time. The proposed 4-month protocol was used to investigate the modulating effects of dietary saturated fat on pancreatic carcinogenesis in hamsters. Hamsters were injected s.c. with 20 mg BOP/kg body wt at 5, 6 and 7 weeks of age. The animals were fed a low fat (LF) control diet (5% lard) or a high fat (HF) diet (20% lard) subsequent to the initiation protocol. At 4 months post-initiation, the pancreata were quantitatively examined for the number and size of putative pre-neoplastic lesions. The major attention was directed to intraductal epithelial hyperplasia of inter/intralobular or main ducts, cystic ductal complexes, tubular ductal complexes and ductal complexes that seemed to be intermediate between the latter two. The number of large ductal complexes of the intermediate and tubular category was significantly greater in hamsters fed a diet with 20% saturated fat as compared to animals maintained on 5% saturated fat. Furthermore, the number of ducts with intraductal hyperplasia was greater in the high fat group, and the proportion of such lesions judged to show atypia was also higher in this group. Dietary fat did not have a significant effect on either the cystic ductal complexes or the incidence of hyperplasia in the main pancreatic duct. These results suggest that a diet high in saturated fat enhances pancreatic carcinogenesis in the BOP-hamster model and, moreover, they suggest that a short-term (4-month) protocol may be useful for evaluation of the effects of potential modulating factors on pancreatic carcinogenesis in Syrian golden hamsters. The utility of the approach should be further evaluated and correlated with the results of long-term studies.