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Carcinogenicity and Mutagenicity Studies with Fluvastatin, a New, Entirely Synthetic HMG-CoA Reductase Inhibitor
Carcinogenicity and Mutagenicity Studies with Fluvastatin, A New, Entirely Synthetic HMG-CoA Reductase Inhibitor. Robison, R. L, Suter, W, and Cox, R. H. (1994). Fundam. Appl. Toxicol. 23, 9-20. The HMG-CoA reductase inhibitors are a new and novel class of cholesterol-lowering agents which are widel...
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Published in: | Fundamental and applied toxicology 1994-07, Vol.23 (1), p.9-20 |
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description | Carcinogenicity and Mutagenicity Studies with Fluvastatin, A New, Entirely Synthetic HMG-CoA Reductase Inhibitor. Robison, R. L, Suter, W, and Cox, R. H. (1994). Fundam. Appl. Toxicol. 23, 9-20.
The HMG-CoA reductase inhibitors are a new and novel class of cholesterol-lowering agents which are widely used worldwide. Fluvastatin is the first entirely synthetic compound in this class and is structurally distinct from fungal metabolite derivatives which are already marketed. As the liver is the site of some toxic effects for these compounds, it was not entirely unexpected that liver cancer was found in rats and/or mice with the first three marketed compounds, lovastatin, pravastatin, and simvastatin. Four lifetime carcinogenicity studies (two rat and two mouse) did not give any evidence that fluvastatin induced liver tumors in rodents. Fluvastatin induced thyroid neoplasms in rats and forestomach papillomas in rodents, as other compounds in this pharmacologic class have also done.
The genotoxic potential of fluvastatin has been assessed in vitro using Salmonella typhimurium, Escherichia coli (gene mutations), V79 Chinese hamster cells (HGPRT gene mutations, chromosomal aberrations), rat hepatocyte primary cultures (DNA repair), and BALB/3T3 cells (malignant transformations). Fluvastatin was also tested in vivo for clastogenicity using the mouse bone marrow micronucleus test and by performing a cytogenetic analysis in the rat bone marrow after acute and subacute treatment. In all seven assays fluvastatin was found to be free of any genotoxic potential. |
doi_str_mv | 10.1006/faat.1994.1073 |
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The HMG-CoA reductase inhibitors are a new and novel class of cholesterol-lowering agents which are widely used worldwide. Fluvastatin is the first entirely synthetic compound in this class and is structurally distinct from fungal metabolite derivatives which are already marketed. As the liver is the site of some toxic effects for these compounds, it was not entirely unexpected that liver cancer was found in rats and/or mice with the first three marketed compounds, lovastatin, pravastatin, and simvastatin. Four lifetime carcinogenicity studies (two rat and two mouse) did not give any evidence that fluvastatin induced liver tumors in rodents. Fluvastatin induced thyroid neoplasms in rats and forestomach papillomas in rodents, as other compounds in this pharmacologic class have also done.
The genotoxic potential of fluvastatin has been assessed in vitro using Salmonella typhimurium, Escherichia coli (gene mutations), V79 Chinese hamster cells (HGPRT gene mutations, chromosomal aberrations), rat hepatocyte primary cultures (DNA repair), and BALB/3T3 cells (malignant transformations). Fluvastatin was also tested in vivo for clastogenicity using the mouse bone marrow micronucleus test and by performing a cytogenetic analysis in the rat bone marrow after acute and subacute treatment. In all seven assays fluvastatin was found to be free of any genotoxic potential.</description><identifier>ISSN: 0272-0590</identifier><identifier>EISSN: 1095-6832</identifier><identifier>DOI: 10.1006/faat.1994.1073</identifier><identifier>PMID: 7958569</identifier><identifier>CODEN: FAATDF</identifier><language>eng</language><publisher>Boston, MA: Elsevier Science (USA)</publisher><subject>3T3 Cells ; Animals ; Anticholesteremic Agents - toxicity ; Bacteria - drug effects ; Biological and medical sciences ; Carcinogenicity Tests ; Carcinogens - toxicity ; Cell Transformation, Neoplastic ; Cells, Cultured - drug effects ; Cricetinae ; Cricetulus ; Cytogenetics ; DNA Repair ; Drug toxicity and drugs side effects treatment ; Fatty Acids, Monounsaturated - toxicity ; Female ; Fluvastatin ; Indoles - toxicity ; Male ; Medical sciences ; Mice ; Mice, Inbred Strains ; Micronucleus Tests ; Miscellaneous (drug allergy, mutagens, teratogens...) ; Mutagenicity Tests ; Mutagens - toxicity ; Pharmacology. Drug treatments ; Rats ; Rats, Inbred Strains</subject><ispartof>Fundamental and applied toxicology, 1994-07, Vol.23 (1), p.9-20</ispartof><rights>1994 Society of Toxicology</rights><rights>1994 INIST-CNRS</rights><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c399t-836af0200477a3c068d322c5373250535d1c677134cc16bd7387ecdc2c1dde613</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=4150685$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/7958569$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Robison, Rodney L.</creatorcontrib><creatorcontrib>Suter, Willi</creatorcontrib><creatorcontrib>Cox, Raymond H.</creatorcontrib><title>Carcinogenicity and Mutagenicity Studies with Fluvastatin, a New, Entirely Synthetic HMG-CoA Reductase Inhibitor</title><title>Fundamental and applied toxicology</title><addtitle>Fundam Appl Toxicol</addtitle><description>Carcinogenicity and Mutagenicity Studies with Fluvastatin, A New, Entirely Synthetic HMG-CoA Reductase Inhibitor. Robison, R. L, Suter, W, and Cox, R. H. (1994). Fundam. Appl. Toxicol. 23, 9-20.
The HMG-CoA reductase inhibitors are a new and novel class of cholesterol-lowering agents which are widely used worldwide. Fluvastatin is the first entirely synthetic compound in this class and is structurally distinct from fungal metabolite derivatives which are already marketed. As the liver is the site of some toxic effects for these compounds, it was not entirely unexpected that liver cancer was found in rats and/or mice with the first three marketed compounds, lovastatin, pravastatin, and simvastatin. Four lifetime carcinogenicity studies (two rat and two mouse) did not give any evidence that fluvastatin induced liver tumors in rodents. Fluvastatin induced thyroid neoplasms in rats and forestomach papillomas in rodents, as other compounds in this pharmacologic class have also done.
The genotoxic potential of fluvastatin has been assessed in vitro using Salmonella typhimurium, Escherichia coli (gene mutations), V79 Chinese hamster cells (HGPRT gene mutations, chromosomal aberrations), rat hepatocyte primary cultures (DNA repair), and BALB/3T3 cells (malignant transformations). Fluvastatin was also tested in vivo for clastogenicity using the mouse bone marrow micronucleus test and by performing a cytogenetic analysis in the rat bone marrow after acute and subacute treatment. In all seven assays fluvastatin was found to be free of any genotoxic potential.</description><subject>3T3 Cells</subject><subject>Animals</subject><subject>Anticholesteremic Agents - toxicity</subject><subject>Bacteria - drug effects</subject><subject>Biological and medical sciences</subject><subject>Carcinogenicity Tests</subject><subject>Carcinogens - toxicity</subject><subject>Cell Transformation, Neoplastic</subject><subject>Cells, Cultured - drug effects</subject><subject>Cricetinae</subject><subject>Cricetulus</subject><subject>Cytogenetics</subject><subject>DNA Repair</subject><subject>Drug toxicity and drugs side effects treatment</subject><subject>Fatty Acids, Monounsaturated - toxicity</subject><subject>Female</subject><subject>Fluvastatin</subject><subject>Indoles - toxicity</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred Strains</subject><subject>Micronucleus Tests</subject><subject>Miscellaneous (drug allergy, mutagens, teratogens...)</subject><subject>Mutagenicity Tests</subject><subject>Mutagens - toxicity</subject><subject>Pharmacology. 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Drug treatments</topic><topic>Rats</topic><topic>Rats, Inbred Strains</topic><toplevel>online_resources</toplevel><creatorcontrib>Robison, Rodney L.</creatorcontrib><creatorcontrib>Suter, Willi</creatorcontrib><creatorcontrib>Cox, Raymond H.</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>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><jtitle>Fundamental and applied toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Robison, Rodney L.</au><au>Suter, Willi</au><au>Cox, Raymond H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Carcinogenicity and Mutagenicity Studies with Fluvastatin, a New, Entirely Synthetic HMG-CoA Reductase Inhibitor</atitle><jtitle>Fundamental and applied toxicology</jtitle><addtitle>Fundam Appl Toxicol</addtitle><date>1994-07-01</date><risdate>1994</risdate><volume>23</volume><issue>1</issue><spage>9</spage><epage>20</epage><pages>9-20</pages><issn>0272-0590</issn><eissn>1095-6832</eissn><coden>FAATDF</coden><abstract>Carcinogenicity and Mutagenicity Studies with Fluvastatin, A New, Entirely Synthetic HMG-CoA Reductase Inhibitor. Robison, R. L, Suter, W, and Cox, R. H. (1994). Fundam. Appl. Toxicol. 23, 9-20.
The HMG-CoA reductase inhibitors are a new and novel class of cholesterol-lowering agents which are widely used worldwide. Fluvastatin is the first entirely synthetic compound in this class and is structurally distinct from fungal metabolite derivatives which are already marketed. As the liver is the site of some toxic effects for these compounds, it was not entirely unexpected that liver cancer was found in rats and/or mice with the first three marketed compounds, lovastatin, pravastatin, and simvastatin. Four lifetime carcinogenicity studies (two rat and two mouse) did not give any evidence that fluvastatin induced liver tumors in rodents. Fluvastatin induced thyroid neoplasms in rats and forestomach papillomas in rodents, as other compounds in this pharmacologic class have also done.
The genotoxic potential of fluvastatin has been assessed in vitro using Salmonella typhimurium, Escherichia coli (gene mutations), V79 Chinese hamster cells (HGPRT gene mutations, chromosomal aberrations), rat hepatocyte primary cultures (DNA repair), and BALB/3T3 cells (malignant transformations). Fluvastatin was also tested in vivo for clastogenicity using the mouse bone marrow micronucleus test and by performing a cytogenetic analysis in the rat bone marrow after acute and subacute treatment. In all seven assays fluvastatin was found to be free of any genotoxic potential.</abstract><cop>Boston, MA</cop><cop>San Diego, CA</cop><cop>New York, NY</cop><pub>Elsevier Science (USA)</pub><pmid>7958569</pmid><doi>10.1006/faat.1994.1073</doi><tpages>12</tpages></addata></record> |
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subjects | 3T3 Cells Animals Anticholesteremic Agents - toxicity Bacteria - drug effects Biological and medical sciences Carcinogenicity Tests Carcinogens - toxicity Cell Transformation, Neoplastic Cells, Cultured - drug effects Cricetinae Cricetulus Cytogenetics DNA Repair Drug toxicity and drugs side effects treatment Fatty Acids, Monounsaturated - toxicity Female Fluvastatin Indoles - toxicity Male Medical sciences Mice Mice, Inbred Strains Micronucleus Tests Miscellaneous (drug allergy, mutagens, teratogens...) Mutagenicity Tests Mutagens - toxicity Pharmacology. Drug treatments Rats Rats, Inbred Strains |
title | Carcinogenicity and Mutagenicity Studies with Fluvastatin, a New, Entirely Synthetic HMG-CoA Reductase Inhibitor |
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