Regeneration of Syrian golden hamster pancreas and covalent binding of N-nitroso-2,6-[3H]dimethylmorpholine
Scarpelli, D.G.; Rao, M.S.; Subbarao, V.; Beversluis, M.
Cancer Research 41(3): 1051-1057
1981
ISSN/ISBN: 0008-5472 PMID: 6161695 Document Number: 175130
The Syrian golden hamster is a potentially useful model for studies of chemically induced pancreatic adenocarcinoma. In an effort to refine the model so its sensitivity to carcinogen can be enhanced such that dose and latent period are decreased and tumor yield increased, experiments were undertaken to induce pancreatic regeneration in the hamster. Random-bred male hamsters given 8 daily i.p. injections of DL-ethionine (500 mg/kg body wt) in 0.9% NaCl solution while on a methionine-deficient diet developed pancreatic injury. Pancreatic regeneration initiated on the 9th day by a single i.p. injection of L-methionine and return to a full amino acid diet led to a gradual increase in wet weight of pancreas, reaching full restitution 17 days later. Mitotic activity, localized largely in acinar cells, rose from a total absence of mitoses on the 8th day to peak value 72 h later, following which it decreased. Uptake of [3H]thymidine limited to acinar cell nuclei was evident 12 h after initiation of regeneration, reached a peak value at 60 h and decreased at 192 h. Pancreatic slices from regenerating (60 h) and normal pancreas were incubated in vitro with 0.1 mM N-nitroso-2,6-[3H]dimethylmorpholine for 90 min. Regenerating pancreas showed increased covalent binding of carcinogen to DNA, RNA and protein as compared to binding observed in normal nonregenerating pancreas. In contrast to the other rodent models of pancreatic regeneration, the hamster responds more rapidly and intensely, suggesting that pancreatic regeneration may be a useful approach toward development of a limited dose schedule for pancreatic carcinogenesis in this species.