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-ini tiation 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 t hen 300 or 100 ppm quinacrine in their diet for 37 weeks. Additional g roups of animals received the BOP injection alone, or only the 300 ppm quinacrine treatment as BOP-negative controls. At week 40 of the expe riment, all surviving animals were killed and development of prolifera tive lesions was assessed histopathologically. The multiplicity of pan creatic adenocarcinomas and dysplastic lesions per hamster was signifi cantly 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 hepato cellular adenomas plus carcinomas was also significantly elevated (P<0 .05) in the BOP/Q300 and BOP/Q100 groups. In contrast, the multiplicit y of lung adenomas plus adenocarcinomas was significantly decreased (P <0.05) by the Q300 treatment. Neither the incidence nor the multiplici ty of renal cell tumors (adenomas and carcinomas) or nephroblastomas s ignificantly differed between the BOP-treated groups. Electron microsc opic examination revealed an abundance of myeloid lamellar bodies fill ing the cytoplasm of hepatocytes and pancreatic ductular and acinar ce lls, and epithelial cells of the gallbladder in the quinacrine-treated animals, the degree being dose-dependent. Our results indicate that q uinacrine enhances pancreatic and hepatic carcinogenesis in hamsters i nduced by BOP.