Hepatocellular Tumor Induction in Heterozygous p53-Deficient CBA Mice by a 26-Week Dietary Administration of Kojic Acid
In order to evaluate the tumorigenic potential of kojic acid (KA), used as a food additive for preventing enzymatic browning of crustaceans and a cosmetic agent for the purpose of skin whitening, heterozygous p53-deficient CBA [p53(+/−)] mice, which are recognized as useful for detecting genotoxic c...
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| Veröffentlicht in: | Toxicological sciences 2003-06, Vol.73 (2), p.287-293 |
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| creator | Takizawa, Tamotsu Mitsumori, Kunitoshi Tamura, Toru Nasu, Masahiro Ueda, Makoto Imai, Toshio Hirose, Masao |
| description | In order to evaluate the tumorigenic potential of kojic acid (KA), used as a food additive for preventing enzymatic browning of crustaceans and a cosmetic agent for the purpose of skin whitening, heterozygous p53-deficient CBA [p53(+/−)] mice, which are recognized as useful for detecting genotoxic carcinogens, and wild-type littermates [p53(+/+) mice] were fed diet containing 0, 1.5, and 3% KA for 26 weeks. KA induced diffuse hypertrophy and hyperplasia of thyroid follicular epithelial cells with decreased serum thyroxine levels in both p53 (+/−) and p53 (+/+) mice, but caused no thyroid tumors. In the liver, the incidence of altered hepatocellular foci was significantly increased at 1.5 and 3% in p 53(+/−) and 1.5% in p53 (+/+) mice, and that of hepatocellular adenomas was increased at 1.5 and 3% in p 53(+/−) and 3% in p53 (+/+) mice. p53 (+/−) mice thus appeared to be more susceptible in terms of the tumorigenic dose of KA with a greater prevalence of hepatic proliferative lesions. The results of the present study indicate tumorigenic potential of KA in the liver, but not thyroid follicular epithelial cells in CBA mice and a contribution of genotoxicity on hepatocellular tumor development cannot be ruled out. |
| doi_str_mv | 10.1093/toxsci/kfg094 |
| format | Article |
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KA induced diffuse hypertrophy and hyperplasia of thyroid follicular epithelial cells with decreased serum thyroxine levels in both p53 (+/−) and p53 (+/+) mice, but caused no thyroid tumors. In the liver, the incidence of altered hepatocellular foci was significantly increased at 1.5 and 3% in p 53(+/−) and 1.5% in p53 (+/+) mice, and that of hepatocellular adenomas was increased at 1.5 and 3% in p 53(+/−) and 3% in p53 (+/+) mice. p53 (+/−) mice thus appeared to be more susceptible in terms of the tumorigenic dose of KA with a greater prevalence of hepatic proliferative lesions. The results of the present study indicate tumorigenic potential of KA in the liver, but not thyroid follicular epithelial cells in CBA mice and a contribution of genotoxicity on hepatocellular tumor development cannot be ruled out.</description><identifier>ISSN: 1096-6080</identifier><identifier>ISSN: 1096-0929</identifier><identifier>EISSN: 1096-0929</identifier><identifier>DOI: 10.1093/toxsci/kfg094</identifier><identifier>PMID: 12700405</identifier><identifier>CODEN: TOSCF2</identifier><language>eng</language><publisher>Cary, NC: Oxford University Press</publisher><subject>Adenoma, Liver Cell - chemically induced ; Adenoma, Liver Cell - genetics ; Adenoma, Liver Cell - pathology ; Administration, Oral ; Animals ; Biological and medical sciences ; Body Weight - drug effects ; Carcinogenesis, carcinogens and anticarcinogens ; Carcinogenicity Tests ; Carcinogens - administration & dosage ; Carcinogens - toxicity ; Chemical agents ; Diet ; Dose-Response Relationship, Drug ; Focal Nodular Hyperplasia - chemically induced ; Focal Nodular Hyperplasia - genetics ; Focal Nodular Hyperplasia - pathology ; Genetic Predisposition to Disease ; hepatocarcinogenesis ; Heterozygote ; heterozygous p53-deficient mice ; kojic acid ; Liver Neoplasms - chemically induced ; Liver Neoplasms - genetics ; Liver Neoplasms - pathology ; Male ; Medical sciences ; Mice ; Mice, Inbred CBA ; Mice, Knockout ; Mycotoxins - administration & dosage ; Mycotoxins - toxicity ; Pyrones - administration & dosage ; Pyrones - toxicity ; Thyroid Gland - drug effects ; Thyroid Gland - pathology ; Tumor Suppressor Protein p53 - deficiency ; Tumor Suppressor Protein p53 - genetics ; Tumors</subject><ispartof>Toxicological sciences, 2003-06, Vol.73 (2), p.287-293</ispartof><rights>2003 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c493t-f1c4fce1be1152593ef1c1942b3ce8fefda0f381e35d98cdbed489868deb083a3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=14863140$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12700405$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Takizawa, Tamotsu</creatorcontrib><creatorcontrib>Mitsumori, Kunitoshi</creatorcontrib><creatorcontrib>Tamura, Toru</creatorcontrib><creatorcontrib>Nasu, Masahiro</creatorcontrib><creatorcontrib>Ueda, Makoto</creatorcontrib><creatorcontrib>Imai, Toshio</creatorcontrib><creatorcontrib>Hirose, Masao</creatorcontrib><title>Hepatocellular Tumor Induction in Heterozygous p53-Deficient CBA Mice by a 26-Week Dietary Administration of Kojic Acid</title><title>Toxicological sciences</title><addtitle>Toxicol. Sci</addtitle><description>In order to evaluate the tumorigenic potential of kojic acid (KA), used as a food additive for preventing enzymatic browning of crustaceans and a cosmetic agent for the purpose of skin whitening, heterozygous p53-deficient CBA [p53(+/−)] mice, which are recognized as useful for detecting genotoxic carcinogens, and wild-type littermates [p53(+/+) mice] were fed diet containing 0, 1.5, and 3% KA for 26 weeks. KA induced diffuse hypertrophy and hyperplasia of thyroid follicular epithelial cells with decreased serum thyroxine levels in both p53 (+/−) and p53 (+/+) mice, but caused no thyroid tumors. In the liver, the incidence of altered hepatocellular foci was significantly increased at 1.5 and 3% in p 53(+/−) and 1.5% in p53 (+/+) mice, and that of hepatocellular adenomas was increased at 1.5 and 3% in p 53(+/−) and 3% in p53 (+/+) mice. p53 (+/−) mice thus appeared to be more susceptible in terms of the tumorigenic dose of KA with a greater prevalence of hepatic proliferative lesions. The results of the present study indicate tumorigenic potential of KA in the liver, but not thyroid follicular epithelial cells in CBA mice and a contribution of genotoxicity on hepatocellular tumor development cannot be ruled out.</description><subject>Adenoma, Liver Cell - chemically induced</subject><subject>Adenoma, Liver Cell - genetics</subject><subject>Adenoma, Liver Cell - pathology</subject><subject>Administration, Oral</subject><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Body Weight - drug effects</subject><subject>Carcinogenesis, carcinogens and anticarcinogens</subject><subject>Carcinogenicity Tests</subject><subject>Carcinogens - administration & dosage</subject><subject>Carcinogens - toxicity</subject><subject>Chemical agents</subject><subject>Diet</subject><subject>Dose-Response Relationship, Drug</subject><subject>Focal Nodular Hyperplasia - chemically induced</subject><subject>Focal Nodular Hyperplasia - genetics</subject><subject>Focal Nodular Hyperplasia - pathology</subject><subject>Genetic Predisposition to Disease</subject><subject>hepatocarcinogenesis</subject><subject>Heterozygote</subject><subject>heterozygous p53-deficient mice</subject><subject>kojic acid</subject><subject>Liver Neoplasms - chemically induced</subject><subject>Liver Neoplasms - genetics</subject><subject>Liver Neoplasms - pathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred CBA</subject><subject>Mice, Knockout</subject><subject>Mycotoxins - administration & dosage</subject><subject>Mycotoxins - toxicity</subject><subject>Pyrones - administration & dosage</subject><subject>Pyrones - toxicity</subject><subject>Thyroid Gland - drug effects</subject><subject>Thyroid Gland - pathology</subject><subject>Tumor Suppressor Protein p53 - deficiency</subject><subject>Tumor Suppressor Protein p53 - genetics</subject><subject>Tumors</subject><issn>1096-6080</issn><issn>1096-0929</issn><issn>1096-0929</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkM9v0zAYhi0EYj_gyBX5ArcwO3ZS-1g6WKcVkGCoaBfLsT9PXpO42I627q8nWyN6-qzPj95P74PQO0o-USLZWQ4Pyfizjbslkr9Ax-OyLogs5cvpXRNBjtBJSneEUFoT-Rod0XJGCCfVMbpfwlbnYKBth1ZHfD10IeLL3g4m-9Bj3-MlZIjhcXcbhoS3FSvOwXnjoc948XmOv3kDuNlhjcu6WANs8LmHrOMOz23ne59y1M9RweGrcOcNnhtv36BXTrcJ3k7zFP3--uV6sSxWPy4uF_NVYbhkuXDUcGeANkBpVVaSwbihkpcNMyAcOKuJY4ICq6wUxjZguZCiFhYaIphmp-jjPncbw98BUladT09tdQ9jH0XFrC5LKUaw2IMmhpQiOLWNvhtrKErUk2m1N632pkf-_RQ8NB3YAz2pHYEPE6CT0a2Lujc-HTguakY5ORweTcHD_38dN6qesVmlln9u1PfVesV__lqrG_YPlAaZLA</recordid><startdate>20030601</startdate><enddate>20030601</enddate><creator>Takizawa, Tamotsu</creator><creator>Mitsumori, Kunitoshi</creator><creator>Tamura, Toru</creator><creator>Nasu, Masahiro</creator><creator>Ueda, Makoto</creator><creator>Imai, Toshio</creator><creator>Hirose, Masao</creator><general>Oxford University Press</general><scope>BSCLL</scope><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></search><sort><creationdate>20030601</creationdate><title>Hepatocellular Tumor Induction in Heterozygous p53-Deficient CBA Mice by a 26-Week Dietary Administration of Kojic Acid</title><author>Takizawa, Tamotsu ; Mitsumori, Kunitoshi ; Tamura, Toru ; Nasu, Masahiro ; Ueda, Makoto ; Imai, Toshio ; Hirose, Masao</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c493t-f1c4fce1be1152593ef1c1942b3ce8fefda0f381e35d98cdbed489868deb083a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Adenoma, Liver Cell - chemically induced</topic><topic>Adenoma, Liver Cell - genetics</topic><topic>Adenoma, Liver Cell - pathology</topic><topic>Administration, Oral</topic><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Body Weight - drug effects</topic><topic>Carcinogenesis, carcinogens and anticarcinogens</topic><topic>Carcinogenicity Tests</topic><topic>Carcinogens - administration & dosage</topic><topic>Carcinogens - toxicity</topic><topic>Chemical agents</topic><topic>Diet</topic><topic>Dose-Response Relationship, Drug</topic><topic>Focal Nodular Hyperplasia - chemically induced</topic><topic>Focal Nodular Hyperplasia - genetics</topic><topic>Focal Nodular Hyperplasia - pathology</topic><topic>Genetic Predisposition to Disease</topic><topic>hepatocarcinogenesis</topic><topic>Heterozygote</topic><topic>heterozygous p53-deficient mice</topic><topic>kojic acid</topic><topic>Liver Neoplasms - chemically induced</topic><topic>Liver Neoplasms - genetics</topic><topic>Liver Neoplasms - pathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred CBA</topic><topic>Mice, Knockout</topic><topic>Mycotoxins - administration & dosage</topic><topic>Mycotoxins - toxicity</topic><topic>Pyrones - administration & dosage</topic><topic>Pyrones - toxicity</topic><topic>Thyroid Gland - drug effects</topic><topic>Thyroid Gland - pathology</topic><topic>Tumor Suppressor Protein p53 - deficiency</topic><topic>Tumor Suppressor Protein p53 - genetics</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Takizawa, Tamotsu</creatorcontrib><creatorcontrib>Mitsumori, Kunitoshi</creatorcontrib><creatorcontrib>Tamura, Toru</creatorcontrib><creatorcontrib>Nasu, Masahiro</creatorcontrib><creatorcontrib>Ueda, Makoto</creatorcontrib><creatorcontrib>Imai, Toshio</creatorcontrib><creatorcontrib>Hirose, Masao</creatorcontrib><collection>Istex</collection><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><jtitle>Toxicological sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Takizawa, Tamotsu</au><au>Mitsumori, Kunitoshi</au><au>Tamura, Toru</au><au>Nasu, Masahiro</au><au>Ueda, Makoto</au><au>Imai, Toshio</au><au>Hirose, Masao</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hepatocellular Tumor Induction in Heterozygous p53-Deficient CBA Mice by a 26-Week Dietary Administration of Kojic Acid</atitle><jtitle>Toxicological sciences</jtitle><addtitle>Toxicol. Sci</addtitle><date>2003-06-01</date><risdate>2003</risdate><volume>73</volume><issue>2</issue><spage>287</spage><epage>293</epage><pages>287-293</pages><issn>1096-6080</issn><issn>1096-0929</issn><eissn>1096-0929</eissn><coden>TOSCF2</coden><abstract>In order to evaluate the tumorigenic potential of kojic acid (KA), used as a food additive for preventing enzymatic browning of crustaceans and a cosmetic agent for the purpose of skin whitening, heterozygous p53-deficient CBA [p53(+/−)] mice, which are recognized as useful for detecting genotoxic carcinogens, and wild-type littermates [p53(+/+) mice] were fed diet containing 0, 1.5, and 3% KA for 26 weeks. KA induced diffuse hypertrophy and hyperplasia of thyroid follicular epithelial cells with decreased serum thyroxine levels in both p53 (+/−) and p53 (+/+) mice, but caused no thyroid tumors. In the liver, the incidence of altered hepatocellular foci was significantly increased at 1.5 and 3% in p 53(+/−) and 1.5% in p53 (+/+) mice, and that of hepatocellular adenomas was increased at 1.5 and 3% in p 53(+/−) and 3% in p53 (+/+) mice. p53 (+/−) mice thus appeared to be more susceptible in terms of the tumorigenic dose of KA with a greater prevalence of hepatic proliferative lesions. The results of the present study indicate tumorigenic potential of KA in the liver, but not thyroid follicular epithelial cells in CBA mice and a contribution of genotoxicity on hepatocellular tumor development cannot be ruled out.</abstract><cop>Cary, NC</cop><pub>Oxford University Press</pub><pmid>12700405</pmid><doi>10.1093/toxsci/kfg094</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Adenoma, Liver Cell - chemically induced Adenoma, Liver Cell - genetics Adenoma, Liver Cell - pathology Administration, Oral Animals Biological and medical sciences Body Weight - drug effects Carcinogenesis, carcinogens and anticarcinogens Carcinogenicity Tests Carcinogens - administration & dosage Carcinogens - toxicity Chemical agents Diet Dose-Response Relationship, Drug Focal Nodular Hyperplasia - chemically induced Focal Nodular Hyperplasia - genetics Focal Nodular Hyperplasia - pathology Genetic Predisposition to Disease hepatocarcinogenesis Heterozygote heterozygous p53-deficient mice kojic acid Liver Neoplasms - chemically induced Liver Neoplasms - genetics Liver Neoplasms - pathology Male Medical sciences Mice Mice, Inbred CBA Mice, Knockout Mycotoxins - administration & dosage Mycotoxins - toxicity Pyrones - administration & dosage Pyrones - toxicity Thyroid Gland - drug effects Thyroid Gland - pathology Tumor Suppressor Protein p53 - deficiency Tumor Suppressor Protein p53 - genetics Tumors |
| title | Hepatocellular Tumor Induction in Heterozygous p53-Deficient CBA Mice by a 26-Week Dietary Administration of Kojic Acid |
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