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Inhibition of Streptozotocin-induced Islet Cell Tumors and N-Nitrosobis(2-oxopropyl)amine-induced Pancreatic Exocrine Tumors in Syrian Hamsters by Exogenous Insulin¹

The Eppley Institute and Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska 68105-1065

The effects of streptozotocin (SZ) and N-nitrosobis(2-oxopropyl)amine (BOP), separately or in combination, on the pancreas, common duct, and gallbladder, all target tissues of BOP, were studied in Syrian golden hamsters. Groups of hamsters were treated with either a single dose (20 mg/kg body weight) of BOP (BOP group), or a single i.p. dose (50 mg/kg body weight) of SZ and 14 days later with a single s.c. injection of the same dose of BOP (SZ + BOP group). Another group of animals was treated similarly with BOP and SZ except that they received twice daily injections of insulin, beginning 1 day after SZ administration and for the duration of the experiment (52 weeks) (SZ + insulin + BOP group). The control group consisted of hamsters treated with a single dose of BOP and daily doses of insulin (insulin + BOP group). Hamsters treated with SZ recovered spontaneously from their diabetes, although the mortality was high (86%). BOP treatment inhibited the diabetogenic effects of SZ in both SZ + BOP and SZ + insulin + BOP groups and reduced the mortality to 43 and 74%, respectively. SZ pretreatment inhibited the incidence of BOP-induced pancreatic ductal/ductular cell carcinomas in the SZ + BOP group (P < 0.01); this protective effect of SZ on carcinoma development was potentiated by additional treatment with insulin (SZ + insulin + BOP group, P < 0.001). Although the frequency of BOP-induced tumors in the gallbladder (all polyps) was not altered by either SZ or insulin, the frequency of the common duct polyps was significantly lower in the SZ + insulin + BOP group than in the BOP group (P < 0.005). Hamsters in the SZ, SZ + BOP, and SZ + insulin + BOP groups developed islet cell adenomas (insulomas). However, the SZ + insulin + BOP group had significantly fewer insulomas than in the SZ + BOP group (P < 0.0005). The overall data confirm the inhibitory effect of SZ on BOP-induced pancreatic cancer and suggest that this effect is related to the diabetic condition of hamsters rather than insulin deficiency and that intact islets appear to be prerequisite for exocrine pancreatic cancer induction by BOP. On the other hand, the inhibitory action of insulin on insuloma induction by SZ and on ductal/ductular cancer induction by BOP seems to be related to the suppressive effect of this hormone on ß-cell and ductal/ductular cell replication, respectively.

¹ Supported by Grant CA38922, Laboratory Core Grant CA36727, National Cancer Institute/NIH, and SIG-16, American Cancer Society.

² To whom requests for reprints should be addressed, at The Eppley Institute for Research in Cancer, University of Nebraska Medical Center, 42nd and Dewey Avenue, Omaha, NE 68105-1065.

Received 5/12/89. Revised 8/ 7/89. Revised 11/13/89. Accepted 11/15/89.

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