Columbano A, Ledda-Columbano G M, Rao P M, Rajalakshmi S, Sarma D S
Am J Pathol. 1984 Sep;116(3):441-6.
A sequential study was performed to investigate the occurrence of cell death in preneoplastic and neoplastic liver cells of F-344 rats. The animals were administered a single initiator dose of 1,2-dimethylhydrazine and were then subjected to a liver carcinogenesis promotion regimen, consisting of a diet containing 1% orotic acid. Cell death, morphologically similar to that described as apoptosis, was evident in foci of preneoplastic hepatocytes at 10 weeks after orotic acid feeding. An increased frequency of apoptotic bodies was observed in nodules, but not in the surrounding liver, 20 weeks after starting the dietary regimen, and in hepatocellular carcinomas that developed after 1 year of continuous promotion. Occurrence of this type of cell death was also observed in liver foci of rats subjected to two other promoting regimens, suggesting, thus, a possible relevance of apoptosis to the carcinogenic process in the liver.
进行了一项序贯研究，以调查F-344大鼠癌前和肿瘤性肝细胞中细胞死亡的发生情况。给动物单次给予1,2-二甲基肼启动剂量，然后进行肝癌发生促进方案，该方案包括含1%乳清酸的饮食。在给予乳清酸10周后，癌前肝细胞灶中出现形态上类似于凋亡的细胞死亡。在开始饮食方案20周后，在结节中观察到凋亡小体频率增加，但在周围肝脏中未观察到，在持续促进1年后发生的肝细胞癌中也观察到凋亡小体频率增加。在接受其他两种促进方案的大鼠肝脏灶中也观察到这种类型的细胞死亡，因此提示凋亡可能与肝脏致癌过程相关。
