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 investigated using a hamster two-stage carcinogenesis model. Male 5-week-old 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 treatment together with cigarette smoke exposure over the same 4-week period. Group 2 was exposed to cigarette smoke for 26 weeks after the BOP-initiation. Groups 3 and 4 were respectively given the BOP-initiation alone and the 26-week cigarette smoke exposure without initiation. Group 5 served as a sham-smoked negative control. The experiment was terminated 30 weeks after the first BOP injection. The incidence of pancreatic adenocarcinomas was significantly decreased in Group 1 as compared 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 proliferative lesions (hyperplasias and papillomas) was significantly increased in Group 2 over Group 3 (P < 0.01). The incidence of pulmonary hyperplasias 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 BOP-initiation phase (Group 1) did not affect the development of respiratory proliferative lesions. No animals in Groups 4 and 5 developed any tumors in the pancreas or respiratory tract. Our results thus indicate that cigarette smoke exposure inhibits pancreatic carcinogenesis when given in the initiation phase, whereas it modulates (enhances or suppresses) the development of proliferative lesions in the respiratory tract if applied during the promotion stage to hamsters pretreated with BOP.
Nishikawa
A
A
Division of Pathology, National Institute of Health Sciences, Tokyo.
Furukawa
F
F
Imazawa
T
T
Yoshimura
H
H
Ikezaki
S
S
Hayashi
Y
Y
Takahashi
M
M
D000818:Animals; D002273:Carcinogens; D003043:Cocarcinogenesis; D006224:Cricetinae; D008297:Male; D008647:Mesocricetus; D009602:Nitrosamines; D010190:Pancreatic Neoplasms / Q000209:etiology*; D010947:Plants, Toxic; D012142:Respiratory Tract Neoplasms / Q000209:etiology*; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana
D002273:Carcinogens; D009602:Nitrosamines; D012906:Smoke; C013622:nitrosobis(2-oxopropyl)amine