Induction of exocrine pancreatic, bile duct, and thyroid gland tumors in offspring of Syrian hamsters treated with N-nitrosobis(2-oxopropyl)amine during pregnancy.

We examined the effect on the Syrian hamster fetal pancrease of N-nitrosobis(2-oxopropyl)amine (BOP), a potent pancreatic carcinogen in adult hamsters. Pregnant Syrian hamsters (F0 generation) were treated with BOP (10 mg/kg body weight) at the 8th, 10th, 12th, and 14th days of gestation (for a total dose of 40 mg/kg body weight). Treatment was well tolerated and all hamsters delivered, at term, pups (F1 generation = 24 females and 27 males) with no abnormalities in number per mother or in physical and behavioral conditions, when compared to matched F1 controls (20 females and 17 males). The experiment was terminated when hamsters in each group (F0 and F1) were 46 weeks old. Pancreatic tumors were found in 89% of the BOP-treated F0 generation and in 5 (50%) of their male litters, but none was seen in their female progeny or in any hamsters from the F1 control group. Tumors in the BOP-treated F0 generation hamsters were ductular adenomas (78%), ductular carcinomas in situ (11%), and ductal/ductular carcinomas (33%). Tumors in their litters were ductular adenomas (20%), ductular carcinomas in situ (10%), and poorly differentiated tumors (20%) that resembled human pancreatoblastomas. The incidence of common duct polyps (44%), gallbladder polyps (44%), and cholangiomas (44%) was significantly higher in the BOP-treated F0 generation than in their litters (which had incidences of 10, 0, and 40%, respectively). Pulmonary and renal neoplasms occurred only in the F0 generation, whereas ovarian and thyroid gland neoplasms were found only in the F1 generation. Results indicate a differing susceptibility of fetal and maternal tissues to BOP.