Sherman C D, Portier C J
Laboratory of Quantitative and Computational Biology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Carcinogenesis. 1995 Oct;16(10):2499-506. doi: 10.1093/carcin/16.10.2499.
The promotional effect of phenobarbital and 1-hydroxymethyl-pyren on enzyme altered lesions in the rat liver were quantified within the framework of two separate multipath/multistage models. The experiment analyzed followed an initiation-promotion protocol in which female Wistar rats were initiated with a single dose of diethylnitrosamine at 0.15 mumol/g body wt followed by a 3 week treatment-free period. A promotor, 1-hydroxymethyl-pyren or phenobarbital was then administered continuously in the diet for 120 days. All animals were sacrificed 3 weeks after treatment and their livers were examined for enzyme histological changes. Focal lesions were classified into three phenotype categories: adenosine triphosphatase altered (ATPase), sulfotransferase altered (ST) and jointly altered lesions (ATPase and ST). Quantitative methods were used to analyze the data, which consisted of the number and sizes of these enzyme-altered lesions. Both multipath/multistage models fitted to the data clearly demonstrate that phenobarbital promotion produced more observable and larger foci than promotion via 1-hydroxymethyl-pyren and that the growth kinetics of the jointly altered lesions were elevated relative to the lesions expressing a single marker. It was not possible with these data to determine if there was a predominant sequence in the formation of jointly altered lesions.
在两个独立的多途径/多阶段模型框架内，对苯巴比妥和1-羟甲基芘对大鼠肝脏酶改变性病变的促进作用进行了定量分析。所分析的实验遵循启动-促进方案，其中雌性Wistar大鼠以0.15 μmol/g体重的单剂量二乙基亚硝胺启动，随后为3周的无处理期。然后在饮食中连续给予促进剂1-羟甲基芘或苯巴比妥120天。在处理后3周处死所有动物，并检查其肝脏的酶组织学变化。局灶性病变分为三种表型类别：三磷酸腺苷酶改变（ATPase）、磺基转移酶改变（ST）和联合改变性病变（ATPase和ST）。使用定量方法分析数据，数据包括这些酶改变性病变的数量和大小。拟合这些数据的两个多途径/多阶段模型均清楚地表明，苯巴比妥促进产生的可观察到的病灶更多且更大，比1-羟甲基芘促进产生的病灶更多，并且联合改变性病变的生长动力学相对于表达单一标志物的病变有所升高。根据这些数据，无法确定联合改变性病变形成过程中是否存在主要序列。
