Biochemical and morphologic studies of heterogeneous lobe responses in hepatocarcinogenesis.
Biochemical and morphologic studies of heterogeneous lobe responses in hepatocarcinogenesis.
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肝癌发生中异质叶反应的生化和形态学研究。
DOI：
10.1093/carcin/7.2.247
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发表时间：
1986
期刊：
影响因子：
4.7
通讯作者：
Swenberg,JA
中科院分区：
文献类型：
--
作者：
Richardson,FC;Boucheron,JA;Dyroff,MC;Popp,JA;Swenberg,JA
实验表明，二乙基亚硝胺（DEN）诱导的肝细胞癌（HCCA）的发病率存在叶间差异，暴露开始后20周，左、右中叶的发病率为100%，右前叶的发病率为30%。这些肿瘤数据提供了一个模型来检验化学诱导的肿瘤形成可以定性和定量地与前致突变DNA损伤和同时的细胞复制相关的假设。在DEN给药0、3、7、14或28天后，通过诱导左右肝中叶和右前叶中生长选择性γ-谷氨酰转移酶阳性（GGT+）病灶，进行实验以测量O 4-乙基脱氧胸苷（O 4-EtdT）（暴露于DEN的大鼠肝DNA中的主要致突变损伤）、N7-乙基鸟嘌呤、细胞复制和肝细胞启动。结果表明，O 4-EtdT浓度始终较高，在左和右中间与右前肝叶，而细胞复制是短暂的较高的右中间和右前叶。同样，在接受Cayama-Farber生长选择方案的DEN暴露大鼠的左中叶和右中叶中观察到大量GGT+病灶。在给予[14 C]DEN后，放射性分布显示出明显的左叶偏好，在4周龄的大鼠，没有事先暴露于DEN和8周龄的大鼠暴露于DEN 4周。这项研究表明，肝细胞启动和HCCA的发病率的叶间差异可能部分是由于细胞复制和DNA烷基化的差异，导致差异DEN分布和/或代谢。
Experiments have demonstrated interlobe differences in the incidence of diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCCA), with a 100% incidence in the left and right median lobes and a 30% incidence in the right anterior lobe 20 weeks after exposure began. These tumor data provide a model to test the hypothesis that chemically induced neoplasia can be qualitatively and quantitatively related to promutagenic DNA damage and concurrent cell replication. Experiments were performed to measure O4-ethyldeoxythymidine (O4-EtdT) (a major pro-mutagenic lesion in hepatic DNA of rats exposed to DEN), N7-ethylguanine, cell replication and hepatocyte initiation using the induction of growthselected γ-glutamyl transferase-positive (GGT+) foci in the left and right median and right anterior hepatic lobes following 0, 3, 7, 14 or 28 days of DEN administration. Results demonstrated that O4-EtdT concentrations were consistently higher in the left and right median versus the right anterior hepatic lobes, while cell replication was transiently higher in the right median and right anterior lobes. Likewise, high numbers of GGT+ foci were observed in the left and right median lobes in DEN-exposed rats subjected to a Cayama-Farber growth selection protocol. Following administration of [14C]DEN, the distribution of radioactivity showed a marked left lobe preference in 4-week-old rats that had no prior exposure to DEN and in 8-week-old rats exposed to DEN for 4 weeks. This study suggests that interlobe differences in hepatocyte initiation and the incidence of HCCA may be due in part to differences in cell replication and in DNA alkylation resulting from differential DEN distribution and/or metabolism.