Furukawa F, Nishikawa A, Enami T, Mitsui M, Imazawa T, Tanakamaru Z, Kim H C, Lee I S, Kasahara K, Takahashi M
Division of Pathology, National Institute of Health Sciences, Tokyo, Japan.
Food Chem Toxicol. 1997 Mar-Apr;35(3-4):387-92. doi: 10.1016/s0278-6915(97)00127-0.
The effects of administration of low doses of 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a tobacco-specific nitrosamine, were investigated in hamsters treated with N-nitrosobis(2-oxopropyl)amine (BOP). Female Syrian golden hamsters were given a single sc injection of BOP at a dose of 10 mg/kg and then administered 2 or 5 ppm NNAL in their drinking water for 52 wk. Additional groups of animals received the BOP injection alone, or only the 2 or 5 ppm NNAL treatments as BOP-negative controls. At wk 53 of the experiment, all surviving animals were killed and the development of proliferative lesions was assessed histopathologically. The total incidence of combined carcinomatous and dysplastic lesions of the exocrine pancreas was significantly higher (P < 0.05) in the BOP/NNAL 5 ppm group than in the BOP alone group, although there was no statistically significant influence of NNAL on the development of either pancreatic adenocarcinomas or dysplastic lesions viewed singly. The treatments with NNAL alone did not induce any proliferative lesions of the exocrine pancreas. No significant intergroup differences were found in either incidence or multiplicity of islet cell proliferative lesions. Immunohistochemical examination of islet cell proliferative lesions (hyperplasias and adenomas) found in the BOP-treated animals showed no significant differences in pancreatic hormone production between NNAL-treated and -untreated groups. The NNAL treatment did not exert any influence on lung, liver or kidney tumorigenesis. Thus, the results suggest that NNAL enhances BOP-induced exocrine but not endocrine pancreatic tumorigenesis in hamsters when given in the post-initiation phase.
研究了烟草特有的亚硝胺4-(甲基亚硝氨基)-1-(3-吡啶基)-1-丁醇(NNAL)低剂量给药对用N-亚硝基双(2-氧代丙基)胺(BOP)处理的仓鼠的影响。雌性叙利亚金仓鼠单次皮下注射10 mg/kg剂量的BOP，然后在其饮用水中给予2或5 ppm的NNAL，持续52周。另外几组动物单独接受BOP注射，或仅接受2或5 ppm NNAL处理作为BOP阴性对照。在实验的第53周，处死所有存活的动物，并通过组织病理学评估增殖性病变的发展。BOP/NNAL 5 ppm组外分泌胰腺的癌性和发育异常性病变合并总发生率显著高于单独BOP组(P < 0.05)，尽管单独来看，NNAL对胰腺腺癌或发育异常性病变的发展没有统计学上的显著影响。单独用NNAL处理未诱导外分泌胰腺出现任何增殖性病变。在胰岛细胞增殖性病变的发生率或多发性方面，未发现组间有显著差异。对BOP处理动物中发现的胰岛细胞增殖性病变(增生和腺瘤)进行免疫组织化学检查发现，NNAL处理组和未处理组之间胰腺激素产生没有显著差异。NNAL处理对肺、肝或肾的肿瘤发生没有任何影响。因此，结果表明，在启动后阶段给予NNAL时，它会增强BOP诱导的仓鼠外分泌胰腺而非内分泌胰腺的肿瘤发生。
