Structural and numerical chromosome aberration inducers in liver micronucleus test in rats with partial hepatectomy
► Chromosome aberration inducers in rat liver micronucleus test are presented. ► Dosing before partial hepatectomy is necessary for structural aberration inducers. ► Dosing after partial hepatectomy is essential for numerical aberration inducers. ► Liver micronucleus induction in rats by colchicine...
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description | ► Chromosome aberration inducers in rat liver micronucleus test are presented. ► Dosing before partial hepatectomy is necessary for structural aberration inducers. ► Dosing after partial hepatectomy is essential for numerical aberration inducers. ► Liver micronucleus induction in rats by colchicine occurred earlier than that in mice.
The liver micronucleus test is an important method to detect pro-mutagens such as active metabolites not reaching bone marrow due to their short lifespan. We have already reported that dosing of the test compound after partial hepatectomy (PH) is essential to detect genotoxicity of numerical chromosome aberration inducers in mice [Mutat. Res. 632 (2007) 89–98]. In naive animals, the proportion of binucleated cells in rats is less than half of that in mice, which suggests a species difference in the response to chromosome aberration inducers. In the present study, we investigated the responses to structural and numerical chromosome aberration inducers in the rat liver micronucleus test. Two structural chromosome aberretion inducers (diethylnitrosamine and 1,2-dimethylhydrazine) and two numerical chromosome aberration inducers (colchicine and carbendazim) were used in the present study. PH was performed a day before or after the dosing of the test compound in 8-week old male F344 rats and hepatocytes were isolated 4 days after the PH. As a result, diethylnitrosamine and 1,2-dimethylhydrazine, structural chromosome aberration inducers, exhibited significant increase in the incidence of micronucleated hepatocyte (MNH) when given either before and after PH. Colchicine and carbendazim, numerical chromosome aberration inducers, did not result in any toxicologically significant increase in MNH frequency when given before PH, while they exhibited MNH induction when given after PH. It is confirmed that dosing after PH is essential in order to detect genotoxicity of numerical chromosome aberration inducers in rats as well as in mice. Regarding the species difference, a different temporal response to colchicine was identified. Colchicine increased the incidence of MNH 4 days after PH in rats, although such induction in mice was observed 8–10 days after PH. |
doi_str_mv | 10.1016/j.mrgentox.2012.04.007 |
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The liver micronucleus test is an important method to detect pro-mutagens such as active metabolites not reaching bone marrow due to their short lifespan. We have already reported that dosing of the test compound after partial hepatectomy (PH) is essential to detect genotoxicity of numerical chromosome aberration inducers in mice [Mutat. Res. 632 (2007) 89–98]. In naive animals, the proportion of binucleated cells in rats is less than half of that in mice, which suggests a species difference in the response to chromosome aberration inducers. In the present study, we investigated the responses to structural and numerical chromosome aberration inducers in the rat liver micronucleus test. Two structural chromosome aberretion inducers (diethylnitrosamine and 1,2-dimethylhydrazine) and two numerical chromosome aberration inducers (colchicine and carbendazim) were used in the present study. PH was performed a day before or after the dosing of the test compound in 8-week old male F344 rats and hepatocytes were isolated 4 days after the PH. As a result, diethylnitrosamine and 1,2-dimethylhydrazine, structural chromosome aberration inducers, exhibited significant increase in the incidence of micronucleated hepatocyte (MNH) when given either before and after PH. Colchicine and carbendazim, numerical chromosome aberration inducers, did not result in any toxicologically significant increase in MNH frequency when given before PH, while they exhibited MNH induction when given after PH. It is confirmed that dosing after PH is essential in order to detect genotoxicity of numerical chromosome aberration inducers in rats as well as in mice. Regarding the species difference, a different temporal response to colchicine was identified. Colchicine increased the incidence of MNH 4 days after PH in rats, although such induction in mice was observed 8–10 days after PH.</description><identifier>ISSN: 1383-5718</identifier><identifier>ISSN: 0027-5107</identifier><identifier>EISSN: 1879-3592</identifier><identifier>DOI: 10.1016/j.mrgentox.2012.04.007</identifier><identifier>PMID: 22561174</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>1,2-Dimethylhydrazine ; Aneugens - toxicity ; Animals ; Benzimidazoles - toxicity ; Bone marrow ; Carbamates - toxicity ; Carbendazim ; Chromosome Aberrations ; Chromosomes ; Colchicine ; Colchicine - analogs & derivatives ; Colchicine - toxicity ; Cytogenetics ; Cytotoxicity ; Diethylnitrosamine ; Diethylnitrosamine - toxicity ; Dimethylhydrazines - toxicity ; DNA Damage ; Dose-Response Relationship, Drug ; Genotoxicity ; Hepatectomy ; Hepatocytes ; Life span ; Liver ; Male ; Metabolites ; Micronucleus test ; Micronucleus Tests - methods ; Mutagenesis ; Mutagens - toxicity ; Mutation ; Numerical chromosome aberration ; Partial hepatectomy ; Rats ; Rats, Inbred F344 ; Rodents ; Structural chromosome aberration ; Toxicology</subject><ispartof>Mutation research, 2012-08, Vol.747 (1), p.98-103</ispartof><rights>2012 Elsevier B.V.</rights><rights>Copyright © 2012 Elsevier B.V. All rights reserved.</rights><rights>Copyright Elsevier BV Aug 30, 2012</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c429t-ad57f793728d444017fb50aa538cf39e7cb3c80e262bf0c2bc1193d19c694d573</citedby><cites>FETCH-LOGICAL-c429t-ad57f793728d444017fb50aa538cf39e7cb3c80e262bf0c2bc1193d19c694d573</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.mrgentox.2012.04.007$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3548,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22561174$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Itoh, Satoru</creatorcontrib><creatorcontrib>Hattori, Chiharu</creatorcontrib><creatorcontrib>Nagata, Mayumi</creatorcontrib><creatorcontrib>Sanbuissho, Atsushi</creatorcontrib><title>Structural and numerical chromosome aberration inducers in liver micronucleus test in rats with partial hepatectomy</title><title>Mutation research</title><addtitle>Mutat Res</addtitle><description>► Chromosome aberration inducers in rat liver micronucleus test are presented. ► Dosing before partial hepatectomy is necessary for structural aberration inducers. ► Dosing after partial hepatectomy is essential for numerical aberration inducers. ► Liver micronucleus induction in rats by colchicine occurred earlier than that in mice.
The liver micronucleus test is an important method to detect pro-mutagens such as active metabolites not reaching bone marrow due to their short lifespan. We have already reported that dosing of the test compound after partial hepatectomy (PH) is essential to detect genotoxicity of numerical chromosome aberration inducers in mice [Mutat. Res. 632 (2007) 89–98]. In naive animals, the proportion of binucleated cells in rats is less than half of that in mice, which suggests a species difference in the response to chromosome aberration inducers. In the present study, we investigated the responses to structural and numerical chromosome aberration inducers in the rat liver micronucleus test. Two structural chromosome aberretion inducers (diethylnitrosamine and 1,2-dimethylhydrazine) and two numerical chromosome aberration inducers (colchicine and carbendazim) were used in the present study. PH was performed a day before or after the dosing of the test compound in 8-week old male F344 rats and hepatocytes were isolated 4 days after the PH. As a result, diethylnitrosamine and 1,2-dimethylhydrazine, structural chromosome aberration inducers, exhibited significant increase in the incidence of micronucleated hepatocyte (MNH) when given either before and after PH. Colchicine and carbendazim, numerical chromosome aberration inducers, did not result in any toxicologically significant increase in MNH frequency when given before PH, while they exhibited MNH induction when given after PH. It is confirmed that dosing after PH is essential in order to detect genotoxicity of numerical chromosome aberration inducers in rats as well as in mice. Regarding the species difference, a different temporal response to colchicine was identified. Colchicine increased the incidence of MNH 4 days after PH in rats, although such induction in mice was observed 8–10 days after PH.</description><subject>1,2-Dimethylhydrazine</subject><subject>Aneugens - toxicity</subject><subject>Animals</subject><subject>Benzimidazoles - toxicity</subject><subject>Bone marrow</subject><subject>Carbamates - toxicity</subject><subject>Carbendazim</subject><subject>Chromosome Aberrations</subject><subject>Chromosomes</subject><subject>Colchicine</subject><subject>Colchicine - analogs & derivatives</subject><subject>Colchicine - toxicity</subject><subject>Cytogenetics</subject><subject>Cytotoxicity</subject><subject>Diethylnitrosamine</subject><subject>Diethylnitrosamine - toxicity</subject><subject>Dimethylhydrazines - toxicity</subject><subject>DNA Damage</subject><subject>Dose-Response Relationship, Drug</subject><subject>Genotoxicity</subject><subject>Hepatectomy</subject><subject>Hepatocytes</subject><subject>Life span</subject><subject>Liver</subject><subject>Male</subject><subject>Metabolites</subject><subject>Micronucleus test</subject><subject>Micronucleus Tests - methods</subject><subject>Mutagenesis</subject><subject>Mutagens - toxicity</subject><subject>Mutation</subject><subject>Numerical chromosome aberration</subject><subject>Partial hepatectomy</subject><subject>Rats</subject><subject>Rats, Inbred F344</subject><subject>Rodents</subject><subject>Structural chromosome aberration</subject><subject>Toxicology</subject><issn>1383-5718</issn><issn>0027-5107</issn><issn>1879-3592</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtv1TAQhS1ERV_8hcoSGzYJYzuJkx2oKg-pEgvateU4E66v4vjiR0v_PY5uy4INK4_l75wZzyHkikHNgHUf9rULP3FN_nfNgfEamhpAviJnrJdDJdqBvy616EXVStafkvMY9wAcBPRvyCnnbceYbM5I_JFCNikHvVC9TnTNDoM15WZ2wTsfvUOqRwxBJ-tXatcpGwyxFHSxDxiosyb4NZsFc6QJY9qeCh3po007etAh2WK3w4NOaJJ3T5fkZNZLxLfP5wW5_3xzd_21uv3-5dv1p9vKNHxIlZ5aOctBSN5PTdMAk_PYgtat6M0sBpRmFKYH5B0fZzB8NIwNYmKD6YamaMUFeX_0PQT_K5fJlLPR4LLoFX2OigHvgUtgbUHf_YPufQ5rmW6jmOhaaDaqO1LlxzEGnNUhWKfDU4HUFovaq5dY1BaLgkaVWIrw6tk-jw6nv7KXHArw8Qhg2ceDxaCisbganGwoS1OTt__r8QcrX6P5</recordid><startdate>20120830</startdate><enddate>20120830</enddate><creator>Itoh, Satoru</creator><creator>Hattori, Chiharu</creator><creator>Nagata, Mayumi</creator><creator>Sanbuissho, Atsushi</creator><general>Elsevier B.V</general><general>Elsevier BV</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7ST</scope><scope>7TM</scope><scope>7U7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>SOI</scope></search><sort><creationdate>20120830</creationdate><title>Structural and numerical chromosome aberration inducers in liver micronucleus test in rats with partial hepatectomy</title><author>Itoh, Satoru ; Hattori, Chiharu ; Nagata, Mayumi ; Sanbuissho, Atsushi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c429t-ad57f793728d444017fb50aa538cf39e7cb3c80e262bf0c2bc1193d19c694d573</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>1,2-Dimethylhydrazine</topic><topic>Aneugens - toxicity</topic><topic>Animals</topic><topic>Benzimidazoles - toxicity</topic><topic>Bone marrow</topic><topic>Carbamates - toxicity</topic><topic>Carbendazim</topic><topic>Chromosome Aberrations</topic><topic>Chromosomes</topic><topic>Colchicine</topic><topic>Colchicine - analogs & derivatives</topic><topic>Colchicine - toxicity</topic><topic>Cytogenetics</topic><topic>Cytotoxicity</topic><topic>Diethylnitrosamine</topic><topic>Diethylnitrosamine - toxicity</topic><topic>Dimethylhydrazines - toxicity</topic><topic>DNA Damage</topic><topic>Dose-Response Relationship, Drug</topic><topic>Genotoxicity</topic><topic>Hepatectomy</topic><topic>Hepatocytes</topic><topic>Life span</topic><topic>Liver</topic><topic>Male</topic><topic>Metabolites</topic><topic>Micronucleus test</topic><topic>Micronucleus Tests - methods</topic><topic>Mutagenesis</topic><topic>Mutagens - toxicity</topic><topic>Mutation</topic><topic>Numerical chromosome aberration</topic><topic>Partial hepatectomy</topic><topic>Rats</topic><topic>Rats, Inbred F344</topic><topic>Rodents</topic><topic>Structural chromosome aberration</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Itoh, Satoru</creatorcontrib><creatorcontrib>Hattori, Chiharu</creatorcontrib><creatorcontrib>Nagata, Mayumi</creatorcontrib><creatorcontrib>Sanbuissho, Atsushi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Environment Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Technology Research Database</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>Environment Abstracts</collection><jtitle>Mutation research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Itoh, Satoru</au><au>Hattori, Chiharu</au><au>Nagata, Mayumi</au><au>Sanbuissho, Atsushi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Structural and numerical chromosome aberration inducers in liver micronucleus test in rats with partial hepatectomy</atitle><jtitle>Mutation research</jtitle><addtitle>Mutat Res</addtitle><date>2012-08-30</date><risdate>2012</risdate><volume>747</volume><issue>1</issue><spage>98</spage><epage>103</epage><pages>98-103</pages><issn>1383-5718</issn><issn>0027-5107</issn><eissn>1879-3592</eissn><abstract>► Chromosome aberration inducers in rat liver micronucleus test are presented. ► Dosing before partial hepatectomy is necessary for structural aberration inducers. ► Dosing after partial hepatectomy is essential for numerical aberration inducers. ► Liver micronucleus induction in rats by colchicine occurred earlier than that in mice.
The liver micronucleus test is an important method to detect pro-mutagens such as active metabolites not reaching bone marrow due to their short lifespan. We have already reported that dosing of the test compound after partial hepatectomy (PH) is essential to detect genotoxicity of numerical chromosome aberration inducers in mice [Mutat. Res. 632 (2007) 89–98]. In naive animals, the proportion of binucleated cells in rats is less than half of that in mice, which suggests a species difference in the response to chromosome aberration inducers. In the present study, we investigated the responses to structural and numerical chromosome aberration inducers in the rat liver micronucleus test. Two structural chromosome aberretion inducers (diethylnitrosamine and 1,2-dimethylhydrazine) and two numerical chromosome aberration inducers (colchicine and carbendazim) were used in the present study. PH was performed a day before or after the dosing of the test compound in 8-week old male F344 rats and hepatocytes were isolated 4 days after the PH. As a result, diethylnitrosamine and 1,2-dimethylhydrazine, structural chromosome aberration inducers, exhibited significant increase in the incidence of micronucleated hepatocyte (MNH) when given either before and after PH. Colchicine and carbendazim, numerical chromosome aberration inducers, did not result in any toxicologically significant increase in MNH frequency when given before PH, while they exhibited MNH induction when given after PH. It is confirmed that dosing after PH is essential in order to detect genotoxicity of numerical chromosome aberration inducers in rats as well as in mice. Regarding the species difference, a different temporal response to colchicine was identified. Colchicine increased the incidence of MNH 4 days after PH in rats, although such induction in mice was observed 8–10 days after PH.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>22561174</pmid><doi>10.1016/j.mrgentox.2012.04.007</doi><tpages>6</tpages></addata></record> |
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subjects | 1,2-Dimethylhydrazine Aneugens - toxicity Animals Benzimidazoles - toxicity Bone marrow Carbamates - toxicity Carbendazim Chromosome Aberrations Chromosomes Colchicine Colchicine - analogs & derivatives Colchicine - toxicity Cytogenetics Cytotoxicity Diethylnitrosamine Diethylnitrosamine - toxicity Dimethylhydrazines - toxicity DNA Damage Dose-Response Relationship, Drug Genotoxicity Hepatectomy Hepatocytes Life span Liver Male Metabolites Micronucleus test Micronucleus Tests - methods Mutagenesis Mutagens - toxicity Mutation Numerical chromosome aberration Partial hepatectomy Rats Rats, Inbred F344 Rodents Structural chromosome aberration Toxicology |
title | Structural and numerical chromosome aberration inducers in liver micronucleus test in rats with partial hepatectomy |
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