Enhancing effects of quinacrine on development of hepatopancreatic lesions in N-nitrosobis(2-oxopropyl)amine-initiated hamsters.
The modifying effects of quinacrine administration during the post-initiation phase of carcinogenesis were investigated in hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP). Female Syrian hamsters were given three weekly s.c. injections of BOP at a dose of 10 mg/kg and then 300 or 100 ppm quinacrine in their diet for 37 weeks. Additional groups of animals received the BOP injection alone, or only the 300 ppm quinacrine treatment as BOP-negative controls. At week 40 of the experiment, all surviving animals were killed and development of proliferative lesions was assessed histopathologically. The multiplicity of pancreatic adenocarcinomas and dysplastic lesions per hamster was significantly higher (P<0.01 and P<0.05) in the BOP/Q100 group (1.92 and 1.78) than in the BOP-alone group (1.07 and 0.79). The incidence of hepatocellular adenomas plus carcinomas was also significantly elevated (P<0.05) in the BOP/Q300 and BOP/Q100 groups. In contrast, the multiplicity of lung adenomas plus adenocarcinomas was significantly decreased (P<0.05) by the Q300 treatment. Neither the incidence nor the multiplicity of renal cell tumors (adenomas and carcinomas) or nephroblastomas significantly differed between the BOP-treated groups. Electron microscopic examination revealed an abundance of myeloid lamellar bodies filling the cytoplasm of hepatocytes and pancreatic ductular and acinar cells, and epithelial cells of the gallbladder in the quinacrine-treated animals, the degree being dose-dependent. Our results indicate that quinacrine enhances pancreatic and hepatic carcinogenesis in hamsters induced by BOP.
Furukawa
F
F
Division of Pathology, National Institute of Health Sciences, Tokyo.
Nishikawa
A
A
Imazawa
T
T
Kasahara
K
K
Takahashi
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D006224:Cricetinae; D004357:Drug Synergism; D005260:Female; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000473:pathology; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D008175:Lung Neoplasms / Q000139:chemically induced / Q000473:pathology; D008647:Mesocricetus; D008854:Microscopy, Electron; D009602:Nitrosamines / Q000633:toxicity*; D009929:Organ Size / Q000187:drug effects; D010190:Pancreatic Neoplasms / Q000139:chemically induced* / Q000473:pathology; D011796:Quinacrine / Q000633:toxicity*
D000970:Antineoplastic Agents; D002273:Carcinogens; D009602:Nitrosamines; C013622:nitrosobis(2-oxopropyl)amine; D011796:Quinacrine