The threshold dose for liver tumor promoting effects of dicyclanil in ICR mice
To determine the threshold dose of dicyclanil (DC) that induces hepatocellular tumor-promoting effects associated with reactive oxygen species (ROS) generation via their metabolic pathways, partial hepatectomized ICR male mice were fed diets containing 0, 187.5, 375 or 750 ppm DC after an intraperit...
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| Veröffentlicht in: | Journal of toxicological sciences 2010/02/01, Vol.35(1), pp.69-78 |
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| creator | Jin, Meilan Dewa, Yasuaki Kawai, Masaomi Nishimura, Jihei Saegusa, Yukie Kemmochi, Sayaka Harada, Tomoaki Shibutani, Makoto Mitsumori, Kunitoshi |
| description | To determine the threshold dose of dicyclanil (DC) that induces hepatocellular tumor-promoting effects associated with reactive oxygen species (ROS) generation via their metabolic pathways, partial hepatectomized ICR male mice were fed diets containing 0, 187.5, 375 or 750 ppm DC after an intraperitoneal injection of N-diethylnitrosamine (DEN) to initiate hepatocarcinogenesis. Immunohistochemically, the proliferating cell nuclear antigen (PCNA)-positive cell ratio was significantly increased in the DEN + 750 ppm DC group compared with the DEN alone group. However, significant increases in the number of γ-glutamyltranspeptidase (GGT)-positive cells and formation of microsomal ROS were not observed in the DEN + DC groups compared with the DEN alone group. Real-time polymerase chain reaction (RT-PCR) showed that the expression of Cyp1a1, Cyp1a2, and OGG1genes was significantly up-regulated in mice given diets containing 375 ppm DC or more, 187.5 ppm DC or more, and 750 ppm DC, respectively. These results suggest that the threshold dose of DC that induces ROS-mediated liver tumor promotion in mice is more than 750 ppm, although expression of the Cyp1a2 gene, which is related to ROS generation, was up-regulated in the liver of mice, even at a DC dose of 187.5 ppm. |
| doi_str_mv | 10.2131/jts.35.69 |
| format | Article |
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Immunohistochemically, the proliferating cell nuclear antigen (PCNA)-positive cell ratio was significantly increased in the DEN + 750 ppm DC group compared with the DEN alone group. However, significant increases in the number of γ-glutamyltranspeptidase (GGT)-positive cells and formation of microsomal ROS were not observed in the DEN + DC groups compared with the DEN alone group. Real-time polymerase chain reaction (RT-PCR) showed that the expression of Cyp1a1, Cyp1a2, and OGG1genes was significantly up-regulated in mice given diets containing 375 ppm DC or more, 187.5 ppm DC or more, and 750 ppm DC, respectively. These results suggest that the threshold dose of DC that induces ROS-mediated liver tumor promotion in mice is more than 750 ppm, although expression of the Cyp1a2 gene, which is related to ROS generation, was up-regulated in the liver of mice, even at a DC dose of 187.5 ppm.</description><identifier>ISSN: 0388-1350</identifier><identifier>EISSN: 1880-3989</identifier><identifier>DOI: 10.2131/jts.35.69</identifier><identifier>PMID: 20118626</identifier><language>eng</language><publisher>Japan: The Japanese Society of Toxicology</publisher><subject>Animals ; Carcinogens - toxicity ; Carcinoma, Hepatocellular - chemically induced ; Carcinoma, Hepatocellular - enzymology ; Carcinoma, Hepatocellular - pathology ; Cytochrome P-450 CYP1A1 - genetics ; Cytochrome P-450 CYP1A2 - genetics ; Dicyclanil ; Diethylnitrosamine - toxicity ; DNA Glycosylases - genetics ; Dose-Response Relationship, Drug ; Drug Therapy, Combination ; gamma-Glutamyltransferase - metabolism ; Gene Expression Regulation, Neoplastic - drug effects ; Hepatectomy ; Juvenile Hormones - toxicity ; Liver Neoplasms - chemically induced ; Liver Neoplasms - enzymology ; Liver Neoplasms - pathology ; Male ; Mice ; Mice, Inbred ICR ; Microsomes, Liver - drug effects ; Microsomes, Liver - metabolism ; Reactive Oxygen Species ; ROS generation ; Threshold dose ; Up-Regulation - drug effects</subject><ispartof>The Journal of Toxicological Sciences, 2010/02/01, Vol.35(1), pp.69-78</ispartof><rights>2010 The Japanese Society of Toxicology</rights><rights>Copyright Japan Science and Technology Agency 2010</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c650t-db1c72d2e36f705f2209c5b43d4062c10c3c1877e0318c270fcbb876516e37223</citedby><cites>FETCH-LOGICAL-c650t-db1c72d2e36f705f2209c5b43d4062c10c3c1877e0318c270fcbb876516e37223</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,1876,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20118626$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Jin, Meilan</creatorcontrib><creatorcontrib>Dewa, Yasuaki</creatorcontrib><creatorcontrib>Kawai, Masaomi</creatorcontrib><creatorcontrib>Nishimura, Jihei</creatorcontrib><creatorcontrib>Saegusa, Yukie</creatorcontrib><creatorcontrib>Kemmochi, Sayaka</creatorcontrib><creatorcontrib>Harada, Tomoaki</creatorcontrib><creatorcontrib>Shibutani, Makoto</creatorcontrib><creatorcontrib>Mitsumori, Kunitoshi</creatorcontrib><title>The threshold dose for liver tumor promoting effects of dicyclanil in ICR mice</title><title>Journal of toxicological sciences</title><addtitle>J Toxicol Sci</addtitle><description>To determine the threshold dose of dicyclanil (DC) that induces hepatocellular tumor-promoting effects associated with reactive oxygen species (ROS) generation via their metabolic pathways, partial hepatectomized ICR male mice were fed diets containing 0, 187.5, 375 or 750 ppm DC after an intraperitoneal injection of N-diethylnitrosamine (DEN) to initiate hepatocarcinogenesis. Immunohistochemically, the proliferating cell nuclear antigen (PCNA)-positive cell ratio was significantly increased in the DEN + 750 ppm DC group compared with the DEN alone group. However, significant increases in the number of γ-glutamyltranspeptidase (GGT)-positive cells and formation of microsomal ROS were not observed in the DEN + DC groups compared with the DEN alone group. Real-time polymerase chain reaction (RT-PCR) showed that the expression of Cyp1a1, Cyp1a2, and OGG1genes was significantly up-regulated in mice given diets containing 375 ppm DC or more, 187.5 ppm DC or more, and 750 ppm DC, respectively. These results suggest that the threshold dose of DC that induces ROS-mediated liver tumor promotion in mice is more than 750 ppm, although expression of the Cyp1a2 gene, which is related to ROS generation, was up-regulated in the liver of mice, even at a DC dose of 187.5 ppm.</description><subject>Animals</subject><subject>Carcinogens - toxicity</subject><subject>Carcinoma, Hepatocellular - chemically induced</subject><subject>Carcinoma, Hepatocellular - enzymology</subject><subject>Carcinoma, Hepatocellular - pathology</subject><subject>Cytochrome P-450 CYP1A1 - genetics</subject><subject>Cytochrome P-450 CYP1A2 - genetics</subject><subject>Dicyclanil</subject><subject>Diethylnitrosamine - toxicity</subject><subject>DNA Glycosylases - genetics</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Therapy, Combination</subject><subject>gamma-Glutamyltransferase - metabolism</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Hepatectomy</subject><subject>Juvenile Hormones - toxicity</subject><subject>Liver Neoplasms - chemically induced</subject><subject>Liver Neoplasms - enzymology</subject><subject>Liver Neoplasms - pathology</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred ICR</subject><subject>Microsomes, Liver - drug effects</subject><subject>Microsomes, Liver - metabolism</subject><subject>Reactive Oxygen Species</subject><subject>ROS generation</subject><subject>Threshold dose</subject><subject>Up-Regulation - drug effects</subject><issn>0388-1350</issn><issn>1880-3989</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90U1rFDEYB_Agil2rB7-ABATFw6x5ksnLXAqy-FIoClLPYSbzpJtlZlKTjNBvb8q2e_DgJQnkx59_8hDyGtiWg4CPh5K3Qm5V94RswBjWiM50T8mGCWMaEJKdkRc5Hxjjmsn2OTnjDMAorjbk-_UeadknzPs4jXSMGamPiU7hDyZa1rmeb1OcYwnLDUXv0ZVMo6djcHdu6pcw0bDQy91POgeHL8kz308ZXz3s5-TXl8_Xu2_N1Y-vl7tPV41TkpVmHMBpPnIUytdKnnPWOTm0YmyZ4g6YEw6M1sgEGFdbezcMRisJCoXmXJyT98fc2u33irnYOWSHUy2Ecc1WC2GkaI2u8t1_JYcWtIL7yLf_wENc01JfYaFVxhhtlKzqw1G5FHNO6O1tCnOf7iwwez8MW4dhhbSqq_bNQ-I6zDie5OPvV3BxBIdc-hs8gT6V4CZ8jILjorrThdv3yeIi_gLFeplh</recordid><startdate>20100201</startdate><enddate>20100201</enddate><creator>Jin, Meilan</creator><creator>Dewa, Yasuaki</creator><creator>Kawai, Masaomi</creator><creator>Nishimura, Jihei</creator><creator>Saegusa, Yukie</creator><creator>Kemmochi, Sayaka</creator><creator>Harada, Tomoaki</creator><creator>Shibutani, Makoto</creator><creator>Mitsumori, Kunitoshi</creator><general>The Japanese Society of Toxicology</general><general>Japan Science and Technology Agency</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>7U7</scope><scope>C1K</scope><scope>SOI</scope><scope>7X8</scope></search><sort><creationdate>20100201</creationdate><title>The threshold dose for liver tumor promoting effects of dicyclanil in ICR mice</title><author>Jin, Meilan ; Dewa, Yasuaki ; Kawai, Masaomi ; Nishimura, Jihei ; Saegusa, Yukie ; Kemmochi, Sayaka ; Harada, Tomoaki ; Shibutani, Makoto ; Mitsumori, Kunitoshi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c650t-db1c72d2e36f705f2209c5b43d4062c10c3c1877e0318c270fcbb876516e37223</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Animals</topic><topic>Carcinogens - toxicity</topic><topic>Carcinoma, Hepatocellular - chemically induced</topic><topic>Carcinoma, Hepatocellular - enzymology</topic><topic>Carcinoma, Hepatocellular - pathology</topic><topic>Cytochrome P-450 CYP1A1 - genetics</topic><topic>Cytochrome P-450 CYP1A2 - genetics</topic><topic>Dicyclanil</topic><topic>Diethylnitrosamine - toxicity</topic><topic>DNA Glycosylases - genetics</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Therapy, Combination</topic><topic>gamma-Glutamyltransferase - metabolism</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Hepatectomy</topic><topic>Juvenile Hormones - toxicity</topic><topic>Liver Neoplasms - chemically induced</topic><topic>Liver Neoplasms - enzymology</topic><topic>Liver Neoplasms - pathology</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred ICR</topic><topic>Microsomes, Liver - drug effects</topic><topic>Microsomes, Liver - metabolism</topic><topic>Reactive Oxygen Species</topic><topic>ROS generation</topic><topic>Threshold dose</topic><topic>Up-Regulation - drug effects</topic><toplevel>online_resources</toplevel><creatorcontrib>Jin, Meilan</creatorcontrib><creatorcontrib>Dewa, Yasuaki</creatorcontrib><creatorcontrib>Kawai, Masaomi</creatorcontrib><creatorcontrib>Nishimura, Jihei</creatorcontrib><creatorcontrib>Saegusa, Yukie</creatorcontrib><creatorcontrib>Kemmochi, Sayaka</creatorcontrib><creatorcontrib>Harada, Tomoaki</creatorcontrib><creatorcontrib>Shibutani, Makoto</creatorcontrib><creatorcontrib>Mitsumori, Kunitoshi</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>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of toxicological sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jin, Meilan</au><au>Dewa, Yasuaki</au><au>Kawai, Masaomi</au><au>Nishimura, Jihei</au><au>Saegusa, Yukie</au><au>Kemmochi, Sayaka</au><au>Harada, Tomoaki</au><au>Shibutani, Makoto</au><au>Mitsumori, Kunitoshi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The threshold dose for liver tumor promoting effects of dicyclanil in ICR mice</atitle><jtitle>Journal of toxicological sciences</jtitle><addtitle>J Toxicol Sci</addtitle><date>2010-02-01</date><risdate>2010</risdate><volume>35</volume><issue>1</issue><spage>69</spage><epage>78</epage><pages>69-78</pages><issn>0388-1350</issn><eissn>1880-3989</eissn><abstract>To determine the threshold dose of dicyclanil (DC) that induces hepatocellular tumor-promoting effects associated with reactive oxygen species (ROS) generation via their metabolic pathways, partial hepatectomized ICR male mice were fed diets containing 0, 187.5, 375 or 750 ppm DC after an intraperitoneal injection of N-diethylnitrosamine (DEN) to initiate hepatocarcinogenesis. Immunohistochemically, the proliferating cell nuclear antigen (PCNA)-positive cell ratio was significantly increased in the DEN + 750 ppm DC group compared with the DEN alone group. However, significant increases in the number of γ-glutamyltranspeptidase (GGT)-positive cells and formation of microsomal ROS were not observed in the DEN + DC groups compared with the DEN alone group. Real-time polymerase chain reaction (RT-PCR) showed that the expression of Cyp1a1, Cyp1a2, and OGG1genes was significantly up-regulated in mice given diets containing 375 ppm DC or more, 187.5 ppm DC or more, and 750 ppm DC, respectively. These results suggest that the threshold dose of DC that induces ROS-mediated liver tumor promotion in mice is more than 750 ppm, although expression of the Cyp1a2 gene, which is related to ROS generation, was up-regulated in the liver of mice, even at a DC dose of 187.5 ppm.</abstract><cop>Japan</cop><pub>The Japanese Society of Toxicology</pub><pmid>20118626</pmid><doi>10.2131/jts.35.69</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Carcinogens - toxicity Carcinoma, Hepatocellular - chemically induced Carcinoma, Hepatocellular - enzymology Carcinoma, Hepatocellular - pathology Cytochrome P-450 CYP1A1 - genetics Cytochrome P-450 CYP1A2 - genetics Dicyclanil Diethylnitrosamine - toxicity DNA Glycosylases - genetics Dose-Response Relationship, Drug Drug Therapy, Combination gamma-Glutamyltransferase - metabolism Gene Expression Regulation, Neoplastic - drug effects Hepatectomy Juvenile Hormones - toxicity Liver Neoplasms - chemically induced Liver Neoplasms - enzymology Liver Neoplasms - pathology Male Mice Mice, Inbred ICR Microsomes, Liver - drug effects Microsomes, Liver - metabolism Reactive Oxygen Species ROS generation Threshold dose Up-Regulation - drug effects |
| title | The threshold dose for liver tumor promoting effects of dicyclanil in ICR mice |
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