Effects of chronic treatment with clofibric acid on response of rat hepatocytes to mitogenic stimuli
Mitoinhibitory effects of clofibric acid (CA) were investigated in rat hepatocytes in vitro and in vivo. Female Sprague-Dawley rats, 11 weeks of age, were dietetically treated with CA at 9000 ppm for up to 13 weeks. In the in vitro study, hepatocytes were isolated from rats on day 4 and in weeks 1,...
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| Veröffentlicht in: | Toxicology letters 1994-11, Vol.74 (2), p.141-148 |
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| creator | Kohji, Tanaka Seiji, Kawamura Hiroyoshi, Matsumoto Kunio, Doi |
| description | Mitoinhibitory effects of clofibric acid (CA) were investigated in rat hepatocytes in vitro and in vivo. Female Sprague-Dawley rats, 11 weeks of age, were dietetically treated with CA at 9000 ppm for up to 13 weeks. In the in vitro study, hepatocytes were isolated from rats on day 4 and in weeks 1, 2, 5, 9 and 13, and cultured for 48 h in a medium containing epidermal growth factor. Over the last 24 h, bromodeoxyuridine (BrdU) was added to the medium to determine number of hepatocytes in S-phase. The labeling index (LI) of CA-treated hepatocytes in culture was below control values as early as day 4, and progressively declined with increasing treatment period. In the in vivo study, rats were 2/3 partially hepatectomized at week 13 and maintained for 24 h. BrdU was injected intraperitoneally 1 h prior to necropsy. The LI in the CA-treated liver was also decreased. These data indicated that continuous treatment of CA resulted in decreases in hepatocyte response to growth stimuli, and suggested a possible relation between the chronic growth inhibitory effect on cell multiplication and tumor promotion in rat hepatocarcinogenesis. |
| doi_str_mv | 10.1016/0378-4274(94)90092-2 |
| format | Article |
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Female Sprague-Dawley rats, 11 weeks of age, were dietetically treated with CA at 9000 ppm for up to 13 weeks. In the in vitro study, hepatocytes were isolated from rats on day 4 and in weeks 1, 2, 5, 9 and 13, and cultured for 48 h in a medium containing epidermal growth factor. Over the last 24 h, bromodeoxyuridine (BrdU) was added to the medium to determine number of hepatocytes in S-phase. The labeling index (LI) of CA-treated hepatocytes in culture was below control values as early as day 4, and progressively declined with increasing treatment period. In the in vivo study, rats were 2/3 partially hepatectomized at week 13 and maintained for 24 h. BrdU was injected intraperitoneally 1 h prior to necropsy. The LI in the CA-treated liver was also decreased. These data indicated that continuous treatment of CA resulted in decreases in hepatocyte response to growth stimuli, and suggested a possible relation between the chronic growth inhibitory effect on cell multiplication and tumor promotion in rat hepatocarcinogenesis.</description><identifier>ISSN: 0378-4274</identifier><identifier>EISSN: 1879-3169</identifier><identifier>DOI: 10.1016/0378-4274(94)90092-2</identifier><identifier>PMID: 7940595</identifier><identifier>CODEN: TOLED5</identifier><language>eng</language><publisher>Shannon: Elsevier Ireland Ltd</publisher><subject>Animals ; Biological and medical sciences ; Cell Division - drug effects ; Cells, Cultured ; Clofibric Acid - administration & dosage ; Drug toxicity and drugs side effects treatment ; Epidermal Growth Factor - antagonists & inhibitors ; Epidermal Growth Factor - pharmacology ; Female ; Hepatectomy ; Liver - cytology ; Liver - drug effects ; Medical sciences ; Miscellaneous (drug allergy, mutagens, teratogens...) ; Mitoinhibition ; Peroxisome proliferators ; Pharmacology. Drug treatments ; Promotion ; Rats ; Rats, Sprague-Dawley</subject><ispartof>Toxicology letters, 1994-11, Vol.74 (2), p.141-148</ispartof><rights>1994</rights><rights>1994 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c417t-8700fc19bf815fe2f6d84031c618e7c70999dac41bc4341d00aaa49864a315f3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/0378427494900922$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4225110$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7940595$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kohji, Tanaka</creatorcontrib><creatorcontrib>Seiji, Kawamura</creatorcontrib><creatorcontrib>Hiroyoshi, Matsumoto</creatorcontrib><creatorcontrib>Kunio, Doi</creatorcontrib><title>Effects of chronic treatment with clofibric acid on response of rat hepatocytes to mitogenic stimuli</title><title>Toxicology letters</title><addtitle>Toxicol Lett</addtitle><description>Mitoinhibitory effects of clofibric acid (CA) were investigated in rat hepatocytes in vitro and in vivo. Female Sprague-Dawley rats, 11 weeks of age, were dietetically treated with CA at 9000 ppm for up to 13 weeks. In the in vitro study, hepatocytes were isolated from rats on day 4 and in weeks 1, 2, 5, 9 and 13, and cultured for 48 h in a medium containing epidermal growth factor. Over the last 24 h, bromodeoxyuridine (BrdU) was added to the medium to determine number of hepatocytes in S-phase. The labeling index (LI) of CA-treated hepatocytes in culture was below control values as early as day 4, and progressively declined with increasing treatment period. In the in vivo study, rats were 2/3 partially hepatectomized at week 13 and maintained for 24 h. BrdU was injected intraperitoneally 1 h prior to necropsy. The LI in the CA-treated liver was also decreased. These data indicated that continuous treatment of CA resulted in decreases in hepatocyte response to growth stimuli, and suggested a possible relation between the chronic growth inhibitory effect on cell multiplication and tumor promotion in rat hepatocarcinogenesis.</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Cell Division - drug effects</subject><subject>Cells, Cultured</subject><subject>Clofibric Acid - administration & dosage</subject><subject>Drug toxicity and drugs side effects treatment</subject><subject>Epidermal Growth Factor - antagonists & inhibitors</subject><subject>Epidermal Growth Factor - pharmacology</subject><subject>Female</subject><subject>Hepatectomy</subject><subject>Liver - cytology</subject><subject>Liver - drug effects</subject><subject>Medical sciences</subject><subject>Miscellaneous (drug allergy, mutagens, teratogens...)</subject><subject>Mitoinhibition</subject><subject>Peroxisome proliferators</subject><subject>Pharmacology. Drug treatments</subject><subject>Promotion</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><issn>0378-4274</issn><issn>1879-3169</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkU9r3DAUxEVJSLdpv0ELOpSQHpxKtqw_l0JZ0jYQyCV3oX1-6qrY1lbSNuTbR2aXPTYgeIf5zSBmCPnI2Q1nXH5lndKNaJW4NuKLYcy0TfuGrLhWpum4NGdkdULeknc5_2GMSSH7C3KhjGC96VdkuPUeoWQaPYVtinMAWhK6MuFc6FMoWwpj9GGTquAgDDTONGHexTnjYkqu0C3uXInwXDDTEukUSvyNS1IuYdqP4T05927M-OF4L8njj9vH9a_m_uHn3fr7fQOCq9JoxZgHbjZe895j6-WgBes4SK5RgWLGmMFVdgOiE3xgzDknjJbCddXQXZKrQ-wuxb97zMVOIQOOo5sx7rNVUqlOCf0qyKWUWskFFAcQUsw5obe7FCaXni1ndhnBLg3bpWFr6ltGsG21fTrm7zcTDifTsfWqfz7qLoMbfXIzhHzCRNv2nLOKfTtgWDv7FzDZDAFnwCGkupkdYvj_P14AZ_yjaA</recordid><startdate>19941101</startdate><enddate>19941101</enddate><creator>Kohji, Tanaka</creator><creator>Seiji, Kawamura</creator><creator>Hiroyoshi, Matsumoto</creator><creator>Kunio, Doi</creator><general>Elsevier Ireland Ltd</general><general>Elsevier Science</general><scope>IQODW</scope><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>7U7</scope><scope>C1K</scope><scope>7X8</scope></search><sort><creationdate>19941101</creationdate><title>Effects of chronic treatment with clofibric acid on response of rat hepatocytes to mitogenic stimuli</title><author>Kohji, Tanaka ; Seiji, Kawamura ; Hiroyoshi, Matsumoto ; Kunio, Doi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c417t-8700fc19bf815fe2f6d84031c618e7c70999dac41bc4341d00aaa49864a315f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Cell Division - drug effects</topic><topic>Cells, Cultured</topic><topic>Clofibric Acid - administration & dosage</topic><topic>Drug toxicity and drugs side effects treatment</topic><topic>Epidermal Growth Factor - antagonists & inhibitors</topic><topic>Epidermal Growth Factor - pharmacology</topic><topic>Female</topic><topic>Hepatectomy</topic><topic>Liver - cytology</topic><topic>Liver - drug effects</topic><topic>Medical sciences</topic><topic>Miscellaneous (drug allergy, mutagens, teratogens...)</topic><topic>Mitoinhibition</topic><topic>Peroxisome proliferators</topic><topic>Pharmacology. Drug treatments</topic><topic>Promotion</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kohji, Tanaka</creatorcontrib><creatorcontrib>Seiji, Kawamura</creatorcontrib><creatorcontrib>Hiroyoshi, Matsumoto</creatorcontrib><creatorcontrib>Kunio, Doi</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>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>MEDLINE - Academic</collection><jtitle>Toxicology letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kohji, Tanaka</au><au>Seiji, Kawamura</au><au>Hiroyoshi, Matsumoto</au><au>Kunio, Doi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of chronic treatment with clofibric acid on response of rat hepatocytes to mitogenic stimuli</atitle><jtitle>Toxicology letters</jtitle><addtitle>Toxicol Lett</addtitle><date>1994-11-01</date><risdate>1994</risdate><volume>74</volume><issue>2</issue><spage>141</spage><epage>148</epage><pages>141-148</pages><issn>0378-4274</issn><eissn>1879-3169</eissn><coden>TOLED5</coden><abstract>Mitoinhibitory effects of clofibric acid (CA) were investigated in rat hepatocytes in vitro and in vivo. Female Sprague-Dawley rats, 11 weeks of age, were dietetically treated with CA at 9000 ppm for up to 13 weeks. In the in vitro study, hepatocytes were isolated from rats on day 4 and in weeks 1, 2, 5, 9 and 13, and cultured for 48 h in a medium containing epidermal growth factor. Over the last 24 h, bromodeoxyuridine (BrdU) was added to the medium to determine number of hepatocytes in S-phase. The labeling index (LI) of CA-treated hepatocytes in culture was below control values as early as day 4, and progressively declined with increasing treatment period. In the in vivo study, rats were 2/3 partially hepatectomized at week 13 and maintained for 24 h. BrdU was injected intraperitoneally 1 h prior to necropsy. The LI in the CA-treated liver was also decreased. These data indicated that continuous treatment of CA resulted in decreases in hepatocyte response to growth stimuli, and suggested a possible relation between the chronic growth inhibitory effect on cell multiplication and tumor promotion in rat hepatocarcinogenesis.</abstract><cop>Shannon</cop><cop>Amsterdam</cop><pub>Elsevier Ireland Ltd</pub><pmid>7940595</pmid><doi>10.1016/0378-4274(94)90092-2</doi><tpages>8</tpages></addata></record> |
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| identifier | ISSN: 0378-4274 |
| ispartof | Toxicology letters, 1994-11, Vol.74 (2), p.141-148 |
| issn | 0378-4274 1879-3169 |
| language | eng |
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| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | Animals Biological and medical sciences Cell Division - drug effects Cells, Cultured Clofibric Acid - administration & dosage Drug toxicity and drugs side effects treatment Epidermal Growth Factor - antagonists & inhibitors Epidermal Growth Factor - pharmacology Female Hepatectomy Liver - cytology Liver - drug effects Medical sciences Miscellaneous (drug allergy, mutagens, teratogens...) Mitoinhibition Peroxisome proliferators Pharmacology. Drug treatments Promotion Rats Rats, Sprague-Dawley |
| title | Effects of chronic treatment with clofibric acid on response of rat hepatocytes to mitogenic stimuli |
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