Peraino C, Fry R J, Staffeldt E, Christopher J P
Cancer Res. 1975 Oct;35(10):2884-90.
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.
早期研究表明，给先前短期喂食2-乙酰氨基芴的大鼠喂食苯巴比妥可增强肝脏肿瘤发生。作为对这种增强作用机制研究的一部分，本研究评估了异戊巴比妥、苯妥英和二氯二苯三氯乙烷（DDT）的相对增强能力，这些物质在对肝脏结构和代谢的影响方面与苯巴比妥有不同程度的相似性。对先喂食2-乙酰氨基芴，随后喂食受试物质（序贯治疗）的大鼠肝脏肿瘤产量进行比较，结果显示异戊巴比妥和苯妥英没有增强活性，而DDT的增强作用与苯巴比妥相似。这些结果表明，序贯治疗技术能够轻易区分增强能力不同的物质，并且在筛选具有这种活性的其他物质时应该会很有用。然后可以将这些物质在肝脏中的比较生化效应与其相对增强能力相关联，以提供与增强作用具体相关的分子事件的信息。本研究通过比较四种受试物质对肝脏重量和DNA合成的影响来启动这种相关性研究。结果显示，增强剂苯巴比妥和DDT均刺激肝脏DNA合成并增加肝脏重量，而非增强剂异戊巴比妥和苯妥英则没有这种作用。苯巴比妥和DDT均增加了早期肿瘤发生率，并且在整个实验过程中肿瘤发生率一直高于其他治疗组，尽管尚不清楚这种增加是否会无限期持续。此外，尽管在所有治疗组中观察到的肿瘤类型范围从高分化到低分化，但在实验的大部分时间里，DDT和苯巴比妥选择性地增加了高分化肿瘤的发生率。
