NicotinamideのN-nitrosobis(2-oxopropyl)amineによるハムスター膵発癌ポストイニシエーション期の抑制

Abstract

Nicotinamide (NA) is synthesized from tryptophan and other amino acids in human bodies, or supplmented foods as one of vitamins. In this study, the chemo- preventive effects of NA on pancreatic duct carcinogenesis initiated with N-nitrosobis(2- oxopropyl)amine (BOP) in Syrian hamsters were investigated. Female 5-week-old ham- sters were given three weekly subcutaneous injections of BOP at a dose of 10 mg/kg body weight followed by 0.5% (Group 1) or 0.2% NA (Group 2) in drinking water for 49 weeks. Additional groups received the BOP injection alone (Group 3), or 0.5% (Group 4) or 0.2% NA (Group 5) in drinking water without BOP injections. Group 6 served as a non-treated control. All animals were sacrificed at 52 weeks after the beginning of the experiment and proliferative lesions in the pancreas were histopathologically assessed. All animals showed no toxic signs including growth retardation. The incidences and multiplicities of dysplastic lesions in the exocrine pancreas were significantly lower (p＜0.05) in Groups 1 and 2 than in Group 3, but NA did not affect the incidence and multiplicity of pancreatic adenocar- cinomas. Morphometrically, the number and area of islets increased in hamsters given NA. Pancreatic hepatocytes appeared in the pancreas of hamsters given BOP and NA but there was no difference in the incidence of these cell populations. In other organs, the incidences and multiplicity of hyperplasia in the lung were more significantly decreased (p＜0.05) in Group 1 than in Group 3, and there was statistically more significant increase (p＜0.05) in the multiplicity of intrahepatic cholangiocellular carcinema in Group 2 than in Group 3. The present results indicate that pancreatic carcinogenesis was inhibited by NA when administered during the post-initiation phase of carcinogenesis by BOP in hamsters.