Laconi E, Vasudevan S, Rao P M, Rajalakshmi S, Pani P, Sarma D S
Department of Pathology, University of Toronto, Ontario, Canada.
Carcinogenesis. 1993 Aug;14(8):1701-4. doi: 10.1093/carcin/14.8.1701.
The present study was designed to determine whether a delay in the start of the promoting regimen after the administration of a carcinogen would influence the promoting efficacy of orotic acid on the development of hepatocellular carcinoma in rats. Male Fischer 344 rats weighing 130-150 g were injected with a single dose of diethylnitrosamine (200 mg/kg body wt i.p.) then divided into 3 groups: groups 1 and 2 were given semi-synthetic basal diet or the same diet containing 1% orotic acid (OA) respectively starting 1 week after the carcinogen; group 3 received the OA diet starting 5 weeks after the administration of diethylnitrosamine. Animals from these 3 groups were sacrificed after 25, 32, 42 and 60 weeks of being fed their respective diets. The results indicated that delaying the start of the OA diet after the carcinogen resulted in about a 50% decrease in the incidence of hepatic nodules and/or hepatocellular carcinomas at various time points during the experiment. This decrease in promoting efficacy of OA was not apparently explainable by lack of metabolic effects of OA, at least in terms of induction of nucleotide pool imbalance, a condition that appears to be important for OA to exert its tumor promoting effects.
本研究旨在确定在给予致癌物后延迟启动促癌方案是否会影响乳清酸对大鼠肝细胞癌发生发展的促癌效果。将体重130 - 150 g的雄性Fischer 344大鼠单次腹腔注射二乙基亚硝胺（200 mg/kg体重），然后分为3组：第1组和第2组分别在给予致癌物1周后开始给予半合成基础饲料或含1%乳清酸（OA）的相同饲料；第3组在给予二乙基亚硝胺5周后开始给予OA饲料。在给予各自饲料25、32、42和60周后，处死这3组动物。结果表明，在给予致癌物后延迟启动OA饲料，导致实验期间各个时间点肝结节和/或肝细胞癌的发生率降低约50%。OA促癌效果的这种降低，至少就诱导核苷酸池失衡而言，显然不能用OA缺乏代谢作用来解释，而核苷酸池失衡这种情况似乎对OA发挥其肿瘤促进作用很重要。
