Comparative enhancing effects of phenobarbital, amobarbital, diphenylhydantoin, and dichlorodiphenyltrichloroethane on 2-acetylaminofluorene-induced hepatic tumorigenesis in the rat.
Comparative enhancing effects of phenobarbital, amobarbital, diphenylhydantoin, and dichlorodiphenyltrichloroethane on 2-acetylaminofluorene-induced hepatic tumorigenesis in the rat.
复制标题
苯巴比妥、异戊巴比妥、二苯基乙内酰脲和二氯二苯基三氯乙烷对 2-乙酰氨基芴诱导的大鼠肝肿瘤发生的比较增强作用。
作者：
C. Peraino;R. Fry;E. Staffeldt;J. Christopher
早期的研究表明，喂食苯巴比妥可促进曾短暂喂饲2-乙酰氨基荧烯的大鼠的肝脏肿瘤形成。作为这种增强机制研究的一部分，本研究评估了异巴比妥、二苯基海因和二氯二苯基三氯乙烷(DDT)的相对增强能力，这些药物在不同程度上类似于苯巴比妥对肝脏结构和代谢的影响。结果表明，异巴比妥和二苯基海因对大鼠肝肿瘤无促进作用，而滴滴涕的促进作用与苯巴比妥相似。这些结果表明，顺序处理技术很容易区分在增强能力方面不同的物质，并应被证明在为这一活性筛选额外物质方面是有用的。然后，这些物质在肝脏中的比较生化效应可以与它们的相对增强能力相关联，以提供与增强特定相关的分子事件的信息。这种相关性是在这项研究中通过比较四种测试物质对肝脏重量和DNA合成的影响而开始的。结果表明，促进剂苯巴比妥和滴滴涕各有促进肝DNA合成和增加肝脏重量的作用，而非促进剂异巴比妥和二苯海因则无此作用。在整个实验过程中，苯巴比妥和滴滴涕都增加了早期肿瘤发生率，并与其他治疗组相比保持了肿瘤发生率的增加，尽管尚不清楚这种增加是否会无限期地持续下去。此外，尽管在所有治疗组中观察到的肿瘤类型从高分化到低分化不等，但在整个实验的大部分时间里，滴滴涕和苯巴比妥选择性地增加了高分化肿瘤的发生率。
Earlier studies showed that phenobarbital feeding enhanced hepatic tumorigenesis in rats previously fed 2-acetylaminofluorene for a brief period. As part of an investigation of the mechanism of this enhancement, the present study evaluated the relative enhancing abilities of amobarbital, diphenylhydantoin, and dichlorodiphenyltrichloroethane (DDT), agents that resemble phenobarbital to varying degrees in their effects on liver structure and metabolism. A comparison of hepatic tumor yields in rats fed 2-acetylaminofluorene, followed by the test substance (sequential treatment), showed that amobarbital and diphenylhydantoin had no enhancing activity, whereas the enhancing effect of DDT was similar to that of phenobarbital. These results show that the sequential treatment technique readily distinguishes among substances differing in enhancing ability and should prove useful in screening additional substances for this activity. The comparative biochemical effects of these substances in the liver can then be correlated with their relative enhancing abilities to provide information on the molecular events specifically associated with enhancement. Such correlations were initiated in this study by comparing the effects of the four test substances on liver weight and DNA synthesis. The results showed that the enhancers, phenobarbital and DDT, each stimulated liver DNA synthesis and increased liver weight, whereas the nonenhancers, amobarbital and diphenylhydantoin, had neither effect. Phenobarbital and DDT both increased the early tumor incidence rate and maintained an increment in tumor incidence over that in the other treatment groups throughout the experiment, although it is not clear whether this increment would persist indefinitely. In addition, although the spectrum of tumor types observed ranged from highly differentiated to poorly differentiated in all treatment groups, DDT and phenobarbital selectively increased the incidence of highly differentiated tumors throughout most of the experiment.
苯巴比妥对肝微粒体酶的剂量相关影响。
DOI：
10.3181/00379727-174-41698
发表时间：
1983
期刊：
Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)
影响因子：
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作者：
Tavoloni,N;Jones,MJ;Berk,PD
通讯作者：
Berk,PD