Heterozygous p53-deficient mice are not susceptible to 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) carcinogenicity
| Autor: | Nobuo Takasuka, Nobuaki Uehara, Hiroyuki Tsuda, Cheol Beom Park, Baba-Toriyama Hiroyasu, Dae Joong Kim |
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| Rok vydání: | 1999 |
| Předmět: |
Male
Cancer Research medicine.medical_specialty Pathology Heterozygote Lung Neoplasms Tumor suppressor gene Ratón Mutagen Biology medicine.disease_cause chemistry.chemical_compound Mice Liver Neoplasms Experimental Internal medicine medicine Animals Carcinogen Gene knockout Alleles Mice Knockout Cocarcinogenesis Dose-Response Relationship Drug Body Weight Wild type Neoplasms Experimental medicine.disease Genes p53 Hemangiosarcoma Endocrinology Oncology chemistry Nitrosamine Hematologic Neoplasms Carcinogens Quinolines Female Tumor Suppressor Protein p53 Mutagens |
| Zdroj: | Cancer letters. 139(2) |
| ISSN: | 0304-3835 |
| Popis: | 2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is a very potent mutagen which induces tumors in the liver, lung and hematopoietic system of CDF1 mice and the liver, Zymbal gland and skin in F344 rats. The recent development of transgenic knockout mice allows their introduction for sensitive screening of environmental carcinogens due to the rapid development of tumors. P53 gene deficient mice (p53-/-) were found to spontaneously develop malignant lymphoma and hemangiosarcoma, whereas heterozygotes (p53+/-) mice display a high incidence of tumors of the urinary bladder when treated with N-butyl-N-(4-hydroxybutyl)nitrosamine. In the present study, to determine whether p53 gene knockout mice can be utilized in a short-term assay model for the screening of heterocyclic amines (HCAs), the effects of MeIQx, as a representative compound, at low doses were examined. Male and female p53+/- mice and wild type littermates (p53+/+) were continuously given diets containing 0, 0.1, 1, 10 and 100 ppm MeIQx for 1 year. No significant difference in tumor induction was observed other than an increase in liver adenomas in males receiving 10 ppm MeIQx treatment. The results indicate that p53+/- mice have no practical advantages for use in short-term carcinogenicity tests of HCAs. |
| Databáze: | OpenAIRE |
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