EFFECTS OF CIGARETTE-SMOKE ON N-NITROSOBIS(2-OXOPROPYL)AMINE-INDUCED PANCREATIC AND RESPIRATORY TUMORIGENESIS IN HAMSTERS

Influences of cigarette smoke on N-nitrosobis(2-oxopropyl)amine (BOP)- induced pancreatic duct and respiratory tract tumorigenesis were inves tigated using a hamster two-stage carcinogenesis model. Male 5-week-ol d hamsters were divided into 5 groups. Group 1 was s.c. injected with BOP at a dose of 10 mg/kg once a week for 3 weeks as an initiation tre atment together with cigarette smoke exposure over the same 4-week per iod. Group 2 was exposed to cigarette smoke for 26 weeks after the BOP -initiation. Groups 3 and 4 were respectively given the POP-initiation alone and the 26-week cigarette smoke exposure without initiation. Gr oup 5 served as a sham-smoked negative control. The experiment was ter minated 30 weeks after the first BOP injection. The incidence of pancr eatic adenocarcinomas was significantly decreased in Group 1 as compar ed to the Group 3 value (P<0.01) while the Group 2 value did not show any change. In contrast, the incidence of laryngeal and tracheal proli ferative lesions (hyperplasias and papillomas) was significantly incre ased in Group 2 over Group 3 (P<0.01). The incidence of pulmonary hype rplasias was also increased in Group 2 over Group 3 (P<0.05), although that of pulmonary adenomas or adenocarcinomas was decreased in Group 2 as compared to the Group 3 value (P<0.01). Cigarette smoke exposure in the POP-initiation phase (Group 1) did not affect the development o f respiratory proliferative lesions. No animals in Groups 4 and 5 deve loped any tumors in the pancreas or respiratory tract. Our results thu s indicate that cigarette smoke exposure inhibits pancreatic carcinoge nesis when given in the initiation phase, whereas it modulates (enhanc es or suppresses) the development of proliferative lesions in the resp iratory tract if applied during the promotion stage to hamsters pretre ated with BOP.