Quantitative analysis of enzyme-altered liver foci in rats initiated with diethylnitrosamine and promoted with 2,3,7,8-tetrachlorodibenzo-p-dioxin or 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin.
Quantitative analysis of enzyme-altered liver foci in rats initiated with diethylnitrosamine and promoted with 2,3,7,8-tetrachlorodibenzo-p-dioxin or 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin.
复制标题
用二乙基亚硝胺启动并用 2,3,7,8-四氯二苯并-对二恶英或 1,2,3,4,6,7,8-七氯二苯并-对二恶英促进的大鼠酶改变肝脏病灶的定量分析。
DOI：
10.1006/taap.1996.0094
复制
发表时间：
1996
影响因子：
3.8
通讯作者：
Bock,KW
中科院分区：
文献类型：
--
作者：
Moolgavkar,SH;Luebeck,EG;Buchmann,A;Bock,KW
在雌性Wistar大鼠肝脏启动促进实验中，采用基于随机模型的定量方法来估计启动率（表达atp酶缺陷表型的改变）和克隆生长的改变细胞。以二乙基亚硝胺（DEN）为引发剂，2,3,7,8-四氯二苯并-对二恶英（TCDD）或1,2,3,4,6,7,8-七氯二苯并-对二恶英（HCDD）为促进剂。随机模型的两个不同版本，称为模型I和模型II，被拟合到数据中。模型1假设，在DEN急性起始的初始阶段之后，DEN治疗的动物和未进行DEN治疗的对照组的背景起始率相等。模型II比模型I更符合数据，它假设即使在急性期结束后，den治疗动物和未接受den治疗的动物的背景起始率也不同。两种模型均表明，TCDD处理后，改变细胞的细胞分裂率和凋亡率均增加。相反，在HCDD治疗期间，细胞分裂率基本保持不变，但细胞凋亡率下降。在HCDD治疗期间，发病背景率与未使用启动子的对照组相同。然而，在TCDD治疗中，从模型中估计的起始率比对照组大大增加。分析还表明，病灶内细胞分裂速率存在异质性，病灶表面细胞分裂速度快于内部细胞分裂速度。
A quantitative method based upon a stochastic model was used to estimate rates of initiation (alteration to express the ATPase-deficient phenotype) and of clonal growth of altered cells in an initiation promotion experiment in the livers of female Wistar rats. Diethylnitrosamine (DEN) was used as the initiating agent followed by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or 1,2,3,4,6,7,8-heptachlorodibenzo-p-dioxin (HCDD) as promoters. Two distinct versions of the stochastic model, called Model I and Model II, were fitted to the data. Model I made the assumption that, after the initial phase of acute initiation with DEN, background rates of initiation were equal in animals treated with DEN and controls that were not so treated. Model II, which fit the data substantially better than Model I, assumed that background rates of initiation were different in DEN-treated animals and animals not so treated, even after the acute phase of initiation was over. Both models indicate that the rates of cell division and apoptosis of altered cells are increased during TCDD treatment. In contrast, the rate of division remains more or less constant during treatment with HCDD, but the rate of apoptosis is decreased. The background rate of initiation during treatment with HCDD is equal to that in controls not administered promoters. With TCDD treatment, however, the rate of initiation estimated from the model is substantially increased over controls. The analysis also suggests that there is heterogeneity within foci of the rates of cell division, with cells on the surface of foci dividing faster than cells in the interior.