Open AccessDifferential Effects of Partial Hepatectomy and Carbon Tetrachloride Administration on Induction of Liver Cell Foci in a Model for Detection of Initiation Activity
Author(s) -
Sakai Hiroki,
Tsukamoto Tetsuya,
Yamamoto Masami,
Shirai Norimitsu,
lidaka Takeshi,
Yanai Tokuma,
Masegi Toshiaki,
Tatematsu Masae
Publication year - 2001
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.2001.tb01055.x
Subject(s) - carbon tetrachloride , hepatocyte , chemistry , carcinogen , isozyme , glutathione , cytochrome p450 , cell growth , microsome , liver cell , microbiology and biotechnology , cell , 2 acetylaminofluorene , biochemistry , metabolism , medicine , enzyme , biology , organic chemistry , in vitro
Differential effects of partial hepatectomy (PH) and carbon tetrachloride (CC1 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 immuno‐blotting (experiment I) after PH or CC1 4 administration. Next, to assess the interrelationships among cell proliferation, fluctuation of CYPs after PH or CC1 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 CC1 4 administration were drastically decreased at the 12‐h tune 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 CC1 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 tune 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 CC1 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.