Effects of Clofibrate in the CB6F1-TgHras2 Mice
スポンサーリンク
概要
- 論文の詳細を見る
The tumorigenic potential of clofibrate, a peroxisome proliferator, was evaluated in a 26-week bioassay using CB6F1-TgHras2 (rasH2) mice carrying a human prototype c-Ha-ras gene. Clofibrate was administered to rasH2 mice orally by gavage at doses of 0 (vehicle control), 125, 250 or 500 mg/kg/day for 26 weeks. Single i.p. injection of 75 mg/kg methyl nitrosourea (MNU) was given to additional rasH2 group as positive control. CB6F1 non-Tg-rasH2 (non-Tg) mice were given either vehicle or 500 mg/kg of clofibrate. In rasH2 mice receiving clofibrate, hepatocellular adenoma was observed in males; 0 (1/15), 125 (0/15), 250 (3/15), and 500 mg/kg (3/15), but not in females. Although the trend test was positive (p<0.01), there was no dose-response and no statistical significance for hepatocellular adenoma. There was no hepatocellular adenoma in non-Tg mice. Increased incidence of neoplastic lesions, e.g. thymic lymphomas, forestomach/skin tumors were found in MNU treated mice as expected. In conclusion, the tumorigenic potential of clofibrate was equivocal in this model, as there was a weak response in the male 250 and 500 mg/kg dose groups but no dose-response. These results indicated further validation of this model as an alternative to the 2-year rodent carcinogenicity bioassay for human carcinogenic safety assessment will be needed.
- 日本毒性病理学会の論文
- 2002-06-30
著者
-
Imai Toshio
Division of Pathology, National Institute of Health Sciences
-
Ando Tomomi
Department of Cardiovascular Surgery, National Cardiovascular Center
-
Aoki Toyohiko
Department Of Developmental Safety Assessment Research Eisai Co. Ltd.
-
Aoki Toyohiko
Department Of Developmental Drug Safety Assessment Research Drug Safety And Disposition Laboratories
-
Imai Toshio
Division Of Pathology National Institute Of Health Science
-
Dodo Tetsushi
Department Of Developmental Drug Safety Assessment Research Drug Safety And Disposition Laboratories
-
KERNS William
Pharma Consulting, Inc.
-
Motooka Satoru
Department Of Pathology Gifu University School Of Medicine
-
Motooka Satoru
Department Of Developmental Drug Safety Assessment Research Drug Safety And Disposition Laboratories
-
Tsukidate Kazuo
Department Of Developmental Drug Safety Assessment Research Drug Safety And Disposition Laboratories
-
Ando Tomomi
Department Of Cardiovascular Surgery National Cardiovascular Center
-
Ando Tomomi
Department Of Developmental Drug Safety Assessment Research Drug Safety And Disposition Laboratories
-
Kerns William
Pharma Consulting Inc.
-
Imai Toshio
Division Of Oncological Pathology Aichi Cancer Center Research Institute
関連論文
- A 55-week chronic toxicity study of dietary administered kojic acid (KA) in male F344 rats
- Increased H-ras mutation frequency in mammary tumors of rats initiated with N-methyl-N-nitrosourea (MNU) and treated with acrylamide
- Lack of modifying effects of prepubertal exposure to acrylamide (AA) on N-methyl-N-nitrosourea (MNU)-induced multi-organ carcinogenesis in F344 rats
- Depression of T cell-mediated immunity reduces sulfadimethoxine-induced capsular inflammation and inhibits associated development of invasive thyroid follicular cell carcinomas in rats
- Lack of enhancement of susceptibility to mammary and thyroid carcinogenesis in rats exposed to DMBA and DHPN following prepubertal iodine deficiency
- Comparison of enhancing effects of different goitrogen treatments in combination with β-estradiol-3-benzoate for establishing a rat two-stage thyroid carcinogenesis model to detect modifying effects of estrogenic compounds
- Lack of Modifying Effects of Combined Treatment of t-butylhydroquinone and Sodium Nitrite on Forestomach Carcinogenesis in rasH2 Mice Initiated with N-ethyl-N-nitrosourea
- Tumorigenic Susceptibility of Catechol on the Gastric Mucosa in rasH2 Mice
- P7-44 Toxicity Evaluation of Bt protein with 28-days dietary administration to gastric-acid reduced rat models(GENERAL TOXICITY)(GENERAL SESSION BY POSTER PRESENTATION)(Proceedings of the 31st Annual Meeting)
- Safety evaluetion of Bt protein by dietary administration to a gastro-intestinal impairment rat model (GENERAL TOXICITY) (GENERAL SESSION BY POSTER PRESENTATION) (Proceedings of the 30th Annual Meeting)
- Difference in the Types of Uterine Tumors between Heterozygous p53-deficient and Wild Type CBA Mice Treated with Ethinylestradiol after N-ethyl-N-nitrosourea Initiation
- Modifying effect of atrazine on DMBA-induced mammary carcinogenesis in ovariectomized rats.(GENERAL SESSION BY POSTER PRESENTATION)(CARCINOGENICITY)
- Enhancing Effects β-Estradiol 3-Benzoate but Not Methoxychlor on the Promotion/Progression Stage of Chemically-induced Mammary Carcinogenesis in Ovariectomized Rats
- GONADAL TOXICITY OF AN ETHANOL EXTRACT OF PSORALEA CORYLIFOLIA IN A RAT 90-DAY REPEATED DOSE STUDY
- Development of invasive follicular cell carcinomas in a rat thyroid carcinogenesis model : Biological impact of capsular inflammation and reduced cyclooxygenase-2 expression
- Coronary Artery Surgery in Patients with Aortitis Syndrome
- Thesaurus for histopathological findings in publically available reports of repeated-dose oral toxicity studies in rats for 156 chemicals
- Possible enhancing effects of atrazine on growth of 7, 12-dimethylbenz(a) anthracene-induced mammary tumors in ovariectomized Sprague-Dawley rats
- Antimutagenic and Anticarcinogenic Properties of Kyo-yasai, Heirloom Vegetables in Kyoto
- Erratum : Thesaurus for histopathological findings in publically available reports of repeated-dose oral toxicity studies in rats for 156 chemicals
- Cardiovascular Assessment of ER-118585, a Selective Phosphodiesterase 5 Inhibitor (Pharmacology)
- Inhibitory effects of aminoguanidine on thyroid follicular carcinoma development in inflamed capsular regions of rats treated with sulfadimethoxine after N-bis(2-hydroxypropyl)nitrosamine-initiation
- Effects of Clofibrate in the CB6F1-TgHras2 Mice
- 21C-02-4 Hepatic Drug Metabolizing Enzymes in CB6F1-TgrasH2 Mice.
- Disappearance of gender-related difference in the toxicity of benzotriazole ultraviolet absorber in juvenile rats
- S13-2 Drug-Induced Vascular Injury in Animals : Mechanisms and the Path Forward(SYMPOSIUM 13: CURRENT STATUS AND FUTURE ASPECTS OF NEW TOXICOLOGICALLY RESPONSIBLE BIOMARKERS)(Proceedings of the 31st Annual Meeting)
- Enzymohistochemical Findings of Four Lines of Transplantable Mouse Osteosarcoma
- Toxic effects of a horseradish extract and allyl isothiocyanate in the urinary bladder after 13-week administration in drinking water to F344 rats
- Susceptibility of Heterozygous p53 Deficient CBA Mice to Induction of Liver Proliferative Lesions by Phenobarbital after Dimethylnitrosamine Initiation
- Antimutagenic and Anticarcinogenic Properties of Kyo-yasai, Heirloom Vegetables in Kyoto