Di(2-ethylhexyl)phthalate induces hepatocellular adenoma in transgenic mice carrying a human prototype c-Ha-ras gene in a 26-week carcinogenicity study

Autor: Kazuo Okimoto, Takatoshi Koujitani, Izuru Kobayashi, Emi Kikawa, Kazuyasu Kijima, Kaoru Toyosawa, Kohji Tanaka, Nobuo Matsuoka, Mami Kohchi
Rok vydání: 2001
Předmět:
Genetically modified mouse
Male
medicine.medical_specialty
Time Factors
Adenoma
040301 veterinary sciences
Ratón
Carcinogenicity Tests
Transgene
Administration
Oral
Mice
Transgenic
Biology
Toxicology
Kidney
030226 pharmacology & pharmacy
Pathology and Forensic Medicine
Adenoma
Liver Cell
0403 veterinary science
03 medical and health sciences
chemistry.chemical_compound
Mice
0302 clinical medicine
Liver Neoplasms
Experimental
Sex Factors
Internal medicine
Diethylhexyl Phthalate
Testis
medicine
Animals
Molecular Biology
Carcinogen
Polymorphism
Single-Stranded Conformational
Dose-Response Relationship
Drug
Phthalate
04 agricultural and veterinary sciences
Cell Biology
Hepatocellular adenoma
medicine.disease
Survival Rate
Endocrinology
Genes
ras
Kidney Tubules
chemistry
Liver
Toxicity
Female
Peroxisome Proliferators
Nasal Cavity
Zdroj: Toxicologic pathology. 29(4)
ISSN: 0192-6233
Popis: To evaluate the transgenic mouse carrying a human prototype c-Ha- ras gene (rasH2 mouse) as a model for 26-week carcinogenicity tests, Di(2-ethylhexyl)phthalate (DEHP), a peroxisome proliferator, was administered to 15 rasH2 mice/sex/group at concentrations of 1,500, 3,000 or 6,000 ppm, and to 15 wild-type (non-Tg) mice/sex/group at a concentration of 6,000 ppm in their diets for 26 weeks. Survival rates and food consumption in the groups treated with DEHP and in the control group were similar. Body weight gain in rasH2 and non-Tg mice at 6,000 ppm in the terminal week decreased about 10% as compared to the control group. Common findings related to treatment with DEHP in rasH2 and non-Tg mice included hypertrophy with coarse granules and deposit of pigment in the liver, hydronephrosi s and tubular regeneration in the kidney, focal atrophy in the testis, and increased eosinophilic body in the nasal cavity. Hepatocellular adenoma was induced by treatment with DEHP, and was confined to male rasH2; mice the incidence being 7%(1/15), 13%(2/15), and 27%(4/15) in the 1,500-, 3,000-, and 6,000-ppm group, respectively. Point mutation was not detected in codon 12 and 61 of human c-Ha- ras transgene upon DNA analyses on frozen samples taken from these hepatocellular adenomas. From the results obtained in this 26-week carcinogenicity study, it is concluded that DEHP is a hepato-carcinogen for transgenic mouse carrying a human prototype c-Ha- ras gene.
Databáze: OpenAIRE
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