INHIBITORY EFFECT OF SARCOPHYTOL-A ON PANCREATIC CARCINOGENESIS AFTERINITIATION BY N-NITROSOBIS(2-OXYPROPYL)AMINE IN SYRIAN-HAMSTERS

Sarcophytol A (SaA), a cembrane-type diterpene, inhibits pancreatic ca rcinogenesis induced by N-nitrosobis(2-oxypropyl)amine (BOP) in hamste rs. The experimental groups received two injections of BOP at 70 mg/kg dose, followed 2 weeks later by a 20 mg/kg dose injection, and were f ed a basal diet or 0.01 and 0.05% SaA diets starting 1 week after the second injection of BOP. Control groups were injected with normal sali ne and fed the basal diet or the 0.05% SaA diet. All animals were kill ed 30 weeks after the start of the experiments. Seventeen POP-treated hamsters fed the basal diet developed pancreatic tumors (77.3%) while only 12 of 21 hamsters fed the 0.01% SaA diet (57.1%) and 12 of 23 ham sters fed the 0.05% SaA diet (52.2%) developed pancreatic tumors. Panc reatic lesions included ductal hyperplasia, atypical ductal hyperplasi a, and carcinoma in situ. Microscopic invasive carcinoma induced by BO P and the incidence of larger pancreatic tumors in hamsters were signi ficantly higher in hamsters fed the basal diet than in hamsters fed th e SaA diet (p < 0.05). The proliferating cell nuclear antigen (PCNA) l abeling index of pancreatic carcinoma in POP-treated hamsters fed the basal diet was 41.2 +/- 13.4%, whereas BOP-treated hamsters fed 0.01 a nd 0.05% SaA diets yielded PCNA indexes of 26.8 +/- 8.3 and 28.4 +/- 7 .0%, respectively. k-ras mutation was detected in 40% of cancers in bo th groups. No pancreatic tumors developed in saline-treated groups, an d no differences in body weights or histological findings in their org ans, including the pancreas, were observed in either group. These find ings suggest that SaA not only inhibits BOP-induced pancreatic carcino genesis in hamsters, but also provides antipromotion and antiprogressi on effects on these tumors, even when SaA commences 1 week after the i nitiation of pancreatic carcinogenesis.