ALTERNATIVE METHODS OF SELECTING RAT HEPATOCELLULAR NODULES RESISTANT TO 2-ACETYLAMINOFLUORENE
ALTERNATIVE METHODS OF SELECTING RAT HEPATOCELLULAR NODULES RESISTANT TO 2-ACETYLAMINOFLUORENE
复制标题
DOI：
10.1002/ijc.2910400512
复制
发表时间：
1987-11-15
影响因子：
6.4
通讯作者：
FARBER, E
中科院分区：
文献类型：
--
作者：
SEMPLEROBERTS, E;HAYES, MA;FARBER, E
饮食2-乙酰氨基芴（2-AFF）加上刺激细胞增殖，如2/3部分肝切除术（PH）或坏死剂量的四氯化碳，经常被用来产生结节的抗性（“启动”）大鼠肝细胞。该方案是一个有用的模型，用于实验分析肝细胞癌变过程中的变化，也作为各种致癌物启动的测定。由于商业来源的含致癌物饮食的可用性减少，我们已经开发了2-AFF给药的替代方法，以在大鼠中产生结节，用N-亚硝基二乙胺开始。本研究比较了通过Solt-Farber程序给予的2-AAF（0.02%饮食，持续2周）与通过管饲给予的2-AAF（作为1%羧甲基纤维素（CMC）水溶液中的混悬液）的结节分泌和促癌功效。每天灌胃给予2-AAF（20 mg/kg/天），然后在第4天给予PH，共4次，其中3次在产生早期耐药结节、晚期持续性结节和肝细胞癌方面与饮食方案相当。这些方案在抑制几乎所有正常肝细胞增殖方面与2-AAF的饮食方案相似。这些方案允许控制2-AAF暴露的持续时间和水平以及所选结节的大小。
Dietary 2-acetylaminofluorene (2-AFF) coupled with a stimulus for cell proliferation such as a 2/3 partial hepatectomy (PH) or a necrotizing dose of carbon tetrachloride is frequently employed to generate nodules of resistant ("initiated") rat hepatocytes. This regimen is a useful model for experimental analysis of alterations in hepatocytes during carcinogenesis, and also as an assay for initiation by various carcinogens. Because of the decreasing availability of carcinogen-containing diets from commercial sources, we have developed alternative methods of 2-AFF administration to generate nodules in rats initiated with N-nitrosodiethylamine. This study compared the nodule-secreting and cancer-promoting efficacy of 2-AAF administered by the Solt-Farber procedure (0.02% in diet for 2 weeks) with 2-AAF administered by gavage, as a suspension in 1% aqueous carboxymethylcellulose (CMC). Three of 4 daily administrations of 2-AAF by gavage (20 mg/kg/day) followed by PH on day 4 were equivalent to the dietary regimen in generating early resistant nodules, late persistent nodules and hepatocellular carcinomas. These regimens were similar to the dietary regimen of 2-AAF in inhibiting virtually all normal hepatocyte proliferation. These regimens permit control over the duration and level of 2-AAF exposure and the resulting size of selected nodules.