Differential Effects of Partial Hepatectomy and Carbon Tetrachloride Administration on Induction of Liver Cell Foci in a Model for Detection of Initiation Activity

Differential effects of partial hepatectomy (PH) and carbon tetrachloride (CC14) 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 fluct...

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Veröffentlicht in:Cancer science 2001-10, Vol.92 (10), p.1018-1025
Hauptverfasser: Sakai, Hiroki, Tsukamoto, Tetsuya, Yamamoto, Masami, Shirai, Norimitsu, lidaka, Takeshi, Yanai, Tokuma, Masegi, Toshiaki, Tatematsu, Masae
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container_end_page 1025
container_issue 10
container_start_page 1018
container_title Cancer science
container_volume 92
creator Sakai, Hiroki
Tsukamoto, Tetsuya
Yamamoto, Masami
Shirai, Norimitsu
lidaka, Takeshi
Yanai, Tokuma
Masegi, Toshiaki
Tatematsu, Masae
description Differential effects of partial hepatectomy (PH) and carbon tetrachloride (CC14) 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 CC14 administration. Next, to assess the interrelationships among cell proliferation, fluctuation of CYPs after PH or CC14 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 CC14 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 CC14 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 CC14 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.
doi_str_mv 10.1111/j.1349-7006.2001.tb01055.x
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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 CC14 administration. Next, to assess the interrelationships among cell proliferation, fluctuation of CYPs after PH or CC14 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 CC14 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 CC14 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 CC14 administration, induction of foci appeared dependent on the recovery of CYP 2E1. 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dosage</topic><topic>Carbon Tetrachloride - pharmacology</topic><topic>Carcinogenesis, carcinogens and anticarcinogens</topic><topic>Cell culture</topic><topic>Cell Division - drug effects</topic><topic>Cell growth</topic><topic>Cell proliferation</topic><topic>Cytochrome P-450 CYP2E1 - genetics</topic><topic>Cytochrome P-450 CYP2E1 - metabolism</topic><topic>Cytochrome P-450 Enzyme System - genetics</topic><topic>Cytochrome P-450 Enzyme System - metabolism</topic><topic>Cytochrome P450</topic><topic>Enzyme Induction - drug effects</topic><topic>Experiments</topic><topic>General aspects</topic><topic>Glutathione</topic><topic>Glutathione Transferase - biosynthesis</topic><topic>GST‐P‐positive foci</topic><topic>Hepatectomy</topic><topic>Hepatocytes</topic><topic>Hepatocytes - cytology</topic><topic>Hepatocytes - drug effects</topic><topic>Hepatocytes - enzymology</topic><topic>Hepatocytes - pathology</topic><topic>Initiation</topic><topic>Isoenzymes</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Medium‐term bioassay</topic><topic>Partial hepatectomy</topic><topic>Placenta</topic><topic>Polymerase chain reaction</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>RNA-directed DNA polymerase</topic><topic>Time Factors</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sakai, Hiroki</creatorcontrib><creatorcontrib>Tsukamoto, Tetsuya</creatorcontrib><creatorcontrib>Yamamoto, Masami</creatorcontrib><creatorcontrib>Shirai, Norimitsu</creatorcontrib><creatorcontrib>lidaka, Takeshi</creatorcontrib><creatorcontrib>Yanai, Tokuma</creatorcontrib><creatorcontrib>Masegi, Toshiaki</creatorcontrib><creatorcontrib>Tatematsu, Masae</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sakai, Hiroki</au><au>Tsukamoto, Tetsuya</au><au>Yamamoto, Masami</au><au>Shirai, Norimitsu</au><au>lidaka, Takeshi</au><au>Yanai, Tokuma</au><au>Masegi, Toshiaki</au><au>Tatematsu, Masae</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Differential Effects of Partial Hepatectomy and Carbon Tetrachloride Administration on Induction of Liver Cell Foci in a Model for Detection of Initiation Activity</atitle><jtitle>Cancer science</jtitle><addtitle>Jpn J Cancer Res</addtitle><date>2001-10</date><risdate>2001</risdate><volume>92</volume><issue>10</issue><spage>1018</spage><epage>1025</epage><pages>1018-1025</pages><issn>0910-5050</issn><issn>1347-9032</issn><eissn>1349-7006</eissn><eissn>1876-4673</eissn><coden>GANNA2</coden><abstract>Differential effects of partial hepatectomy (PH) and carbon tetrachloride (CC14) 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 CC14 administration. Next, to assess the interrelationships among cell proliferation, fluctuation of CYPs after PH or CC14 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 CC14 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 CC14 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 CC14 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.</abstract><cop>Oxford, UK</cop><pub>Blackwell Publishing Ltd</pub><pmid>11676851</pmid><doi>10.1111/j.1349-7006.2001.tb01055.x</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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source Wiley Online Library - AutoHoldings Journals; MEDLINE; IngentaConnect Free/Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central
subjects Animals
Apoenzymes - metabolism
Biological and medical sciences
Blotting, Western
Bromodeoxyuridine
Carbon tetrachloride
Carbon Tetrachloride - administration & dosage
Carbon Tetrachloride - pharmacology
Carcinogenesis, carcinogens and anticarcinogens
Cell culture
Cell Division - drug effects
Cell growth
Cell proliferation
Cytochrome P-450 CYP2E1 - genetics
Cytochrome P-450 CYP2E1 - metabolism
Cytochrome P-450 Enzyme System - genetics
Cytochrome P-450 Enzyme System - metabolism
Cytochrome P450
Enzyme Induction - drug effects
Experiments
General aspects
Glutathione
Glutathione Transferase - biosynthesis
GST‐P‐positive foci
Hepatectomy
Hepatocytes
Hepatocytes - cytology
Hepatocytes - drug effects
Hepatocytes - enzymology
Hepatocytes - pathology
Initiation
Isoenzymes
Male
Medical sciences
Medium‐term bioassay
Partial hepatectomy
Placenta
Polymerase chain reaction
Rats
Rats, Inbred F344
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
RNA, Messenger - metabolism
RNA-directed DNA polymerase
Time Factors
Tumors
title Differential Effects of Partial Hepatectomy and Carbon Tetrachloride Administration on Induction of Liver Cell Foci in a Model for Detection of Initiation Activity
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