在一个用于检测启动活性的模型中，部分肝切除术和给予四氯化碳对肝细胞灶诱导的不同影响。

Differential effects of partial hepatectomy and carbon tetrachloride administration on induction of liver cell foci in a model for detection of initiation activity.

作者信息

Sakai H, Tsukamoto T, Yamamoto M, Shirai N, Iidaka T, Yanai T, Masegi T, Tatematsu M

机构信息

Division of Oncological Pathology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681.

出版信息

Jpn J Cancer Res. 2001 Oct;92(10):1018-25. doi: 10.1111/j.1349-7006.2001.tb01055.x.

DOI:10.1111/j.1349-7006.2001.tb01055.x

PMID:11676851

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5926621/

Abstract

Differential effects of partial hepatectomy (PH) and carbon tetrachloride (CCl(4)) administration on induction of glutathione S-transferase placental form (GST-P)-positive foci were investigated in a model for detection of initiation activity. Firstly, we surveyed cell proliferation kinetics and fluctuation in cytochrome P450 (CYP) mRNA levels by means of relative-quantitative real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and CYP 2E1 apoprotein amount by immunoblotting (experiment I) after PH or CCl(4) administration. Next, to assess the interrelationships among cell proliferation, fluctuation of CYPs after PH or CCl(4) administration and induction of liver cell foci, the non-hepatocarcinogen, 1,2-dimethylhydrazine (DMH) was administered to 7-week-old male F344 rats and initiated populations were selected using the resistant hepatocyte model (experiment II). In experiment I, the values of all CYP isozyme mRNAs after PH or CCl(4) administration were drastically decreased at the 12-h time point. From 72 h, mRNAs for all CYP isozymes began increasing, with complete recovery after 7 days. The CYP 2E1 apoprotein content in the PH group fluctuated weakly, whereas in the CCl(4) group it had decreased rapidly after 12 h and was still low at the 48 h point. In experiment II, induction of GST-P-positive foci was related to cell kinetics in the PH group, with about a 6-h time lag between time for carcinogen administration giving greatest induction of GST-P-positive foci and peaks in bromodeoxyuridine (BrdU) labeling, presumably due to the necessity for bioactivation of DMH. With CCl(4) administration, induction of foci appeared dependent on the recovery of CYP 2E1. In conclusion, PH was able to induce cell proliferation with maintenance of CYP 2E1, therefore being advantageous for induction of liver cell foci in models to detect initiation activity.

摘要

在一个检测启动活性的模型中，研究了部分肝切除术（PH）和给予四氯化碳（CCl₄）对谷胱甘肽S-转移酶胎盘型（GST-P）阳性灶诱导的不同影响。首先，我们通过相对定量实时逆转录聚合酶链反应（RT-PCR）调查了PH或CCl₄给药后细胞增殖动力学以及细胞色素P450（CYP）mRNA水平的波动，并通过免疫印迹法检测了CYP 2E1载脂蛋白的量（实验I）。接下来，为了评估PH或CCl₄给药后细胞增殖、CYPs波动与肝细胞灶诱导之间的相互关系，将非致癌剂1,2-二甲基肼（DMH）给予7周龄雄性F344大鼠，并使用抗性肝细胞模型选择起始群体（实验II）。在实验I中，PH或CCl₄给药后所有CYP同工酶mRNA的值在12小时时间点急剧下降。从72小时开始，所有CYP同工酶的mRNA开始增加，7天后完全恢复。PH组中CYP 2E1载脂蛋白含量波动较小，而在CCl₄组中，12小时后迅速下降，在48小时时仍较低。在实验II中，GST-P阳性灶的诱导与PH组中的细胞动力学有关，在给予致癌物后诱导GST-P阳性灶的时间与溴脱氧尿苷（BrdU）标记的峰值之间大约有6小时的时间滞后，这可能是由于DMH生物活化的必要性。给予CCl₄后，灶的诱导似乎依赖于CYP 2E1的恢复。总之，PH能够在维持CYP 2E1的情况下诱导细胞增殖，因此在检测启动活性的模型中有利于诱导肝细胞灶。