Phenotypically selective promotion of diethylnitrosamine-initiated altered hepatocyte foci by dietary phenobarbital or a topically applied coal-derived organic mixture in male and female rats.
Phenotypically selective promotion of diethylnitrosamine-initiated altered hepatocyte foci by dietary phenobarbital or a topically applied coal-derived organic mixture in male and female rats.
复制标题
在雄性和雌性大鼠中，通过饮食苯巴比妥或局部应用煤衍生的有机混合物，对二乙基亚硝胺引发的肝细胞病灶改变进行表型选择性促进。
DOI：
10.1016/0304-3835(87)90155-8
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发表时间：
1987
期刊：
影响因子：
9.7
通讯作者：
Mahlum,DD
中科院分区：
文献类型：
--
作者：
Peraino,C;Haugen,DA;Carnes,BA;ReillyJr,CA;Springer,DL;Mahlum,DD
在雄性和雌性大鼠中，研究了二乙基亚硝胺（DEN）引发的肝细胞改变灶的相对频率，这些肝细胞改变灶是由于膳食苯巴比妥或局部应用的煤源性有机混合物（CDM）的促进作用而出现的。检查病灶人群的两种组织化学标志物，γ-谷氨酰转肽酶[GG（+）]和铁排斥[FE（−）]升高，产生3种可检测的病灶表型，即GG（+）病灶、FE（−）病灶和GG（+）（FE（−）病灶。通过使用连续冰冻切片和计算机辅助图像分析来定量这3种表型的频率。与我们先前的观察结果一致，皮肤暴露于CDM或饮食苯巴比妥促进了DEN引发的病灶的表达。然而，目前的数据表明，CDM的这种促进作用仅发生在女性中，并仅限于GG（+）FE（-）表型的病灶。另一方面，膳食苯巴比妥促进GG（+）和GG（+）FE（-）表型，对雄性和雌性均有效，但也观察到苯巴比妥促进效率的性别相关差异。3种焦点表型的反应中的显著异质性表明，每种表型是特定类型的基因组改变的结果，其具有响应于给定的促进刺激而进行表型表达的特定能力。
Relative frequencies of diethylnitrosamine (DEN)-initiated foci of altered hepatocytes appearing in response to promotion by either dietary phenobarbital or a topically applied coal-derived organic mixture (CDM) were investigated in male and female rats. The focus population was examined for two histochemical markers, elevated gamma-glutamyl transpeptidase [GG (+)] and iron exclusion [FE (−)], giving rise to 3 detectable focus phenotypes, ie, GG (+) foci, FE (−) foci, and GG (+)(FE (−) foci. Frequencies of the 3 phenotypes were quantitated through the use of serial frozen sectioning and computer-assisted image analysis. In agreement with our prior observations, cutaneous exposure to CDM or dietary phenobarbital promoted the expression of DEN-initiated foci. However, the current data showed that this promoting effect of CDM occurred only in females and was restricted to foci with the GG (+) FE (−) phenotype. Dietary phenobarbital, on the other hand, promoted both the GG (+) and GG (+) FE (−) phenotypes and was effective in both males and females, althouth a sex-related differential in the promoting efficiency of phenobarbital was also observed. The pronounced heterogeneity in the responses of the 3 focus phenotypes suggests that each phenotype is the consequence of a specific type of genomic alteration with a specific capacity to undergo phenotypic expression in response to a given promoting stimulus.