Laconi E, Vasudevan S, Rao P M, Rajalakshmi S, Sarma D S
Toxicol Pathol. 1987;15(2):198-201. doi: 10.1177/019262338701500212.
A delay in the exposure of initiated rats to orotic acid (OA) beyond a specific time frame results in a progressive loss of promotional effect in liver carcinogenesis. The current study was designed to ascertain whether the loss of promotional effect could be counteracted by pre-exposing the initiated animals to other rat liver promoting regimens such as a diet deficient in choline (CD). Male Fischer 344 rats (150 g) were initiated with diethylnitrosamine (200 mg/kg, ip); 1 week later they were given either a CD diet or a CD diet supplemented with choline for 5 weeks. Animals from these two groups were then fed either a 1% OA diet or the basal diet for another 20 weeks. The results indicated that the loss of OAs promotion efficacy from delaying the start of the promoting regimen can be counteracted by pre-exposing the initiated rats to a CD diet. Thus in rats exposed to OA from the first week of initiation, 7% of the liver developed as nodular areas, whereas only 0.8% of liver was nodular when OA feeding was delayed by 5 weeks. This loss was abolished when initiated rats were fed a CD diet for 5 weeks prior to feeding OA for 20 weeks. These results suggest that in a rat liver tumor promotion model, two tumor promoters, OA and CD, show some degree of complementarity when given sequentially.
在特定时间框架之后延迟给已启动的大鼠喂食乳清酸（OA）会导致肝癌发生中促癌作用的逐渐丧失。本研究旨在确定预先将已启动的动物暴露于其他大鼠肝脏促癌方案（如胆碱缺乏饮食（CD））是否可以抵消促癌作用的丧失。雄性Fischer 344大鼠（150克）用二乙基亚硝胺（200毫克/千克，腹腔注射）启动；1周后，它们被给予CD饮食或补充胆碱的CD饮食5周。然后将这两组动物再分别喂食1% OA饮食或基础饮食20周。结果表明，通过预先将已启动的大鼠暴露于CD饮食，可以抵消因延迟启动促癌方案而导致的OA促癌功效的丧失。因此，在从启动第一周就暴露于OA的大鼠中，7%的肝脏发展为结节区域，而当OA喂食延迟5周时，只有0.8%的肝脏出现结节。当已启动的大鼠在喂食OA 20周之前先喂食CD饮食5周时，这种丧失就被消除了。这些结果表明，在大鼠肝癌促癌模型中，两种肿瘤促癌剂OA和CD依次给予时表现出一定程度的互补性。
