Frequent p53 and H-ras Mutations in Benzene- and Ethylene Oxide-Induced Mammary Gland Carcinomas from B6C3F1 Mice
| Autor: | Robert C. Sills, Thai-Vu T. Ton, Natasha P. Clayton, Hue-Hua L. Hong, Christopher D. Houle, James Huff |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Ethylene Oxide
Ethylene Tumor suppressor gene 040301 veterinary sciences Ratón DNA Mutational Analysis Mammary gland Mammary Neoplasms Animal Biology Toxicology medicine.disease_cause Polymerase Chain Reaction 030226 pharmacology & pharmacy Pathology and Forensic Medicine Rodent Diseases 0403 veterinary science Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Animals Codon Molecular Biology Carcinogen Mutation Ethylene oxide Mammary Neoplasms Experimental Benzene Exons 04 agricultural and veterinary sciences Cell Biology Immunohistochemistry Gene Expression Regulation Neoplastic Genes ras medicine.anatomical_structure chemistry Carcinogens Cancer research Female Tumor Suppressor Protein p53 |
| Zdroj: | Toxicologic Pathology. 34:752-762 |
| ISSN: | 1533-1601 0192-6233 |
| DOI: | 10.1080/01926230600935912 |
| Popis: | Benzene and ethylene oxide are multisite carcinogens in rodents and classified as human carcinogens by the National Toxicology Program. In 2-year mouse studies, both chemicals induced mammary carcinomas. We examined spontaneous, benzene-, and ethylene oxide-induced mouse mammary carcinomas for p53 protein expression, using immunohistochemistry, and p53 (exons 5–8) and H -ras (codon 61) mutations using cycle sequencing techniques. p53 protein expression was detected in 42% (8/19) of spontaneous, 43% (6/14) of benzene-, and 67% (8/12) of ethylene oxide-induced carcinomas. However, semiquantitative evaluation of p53 protein expression revealed that benzene- and ethylene oxide-induced carcinomas exhibited expression levels five- to six-fold higher than spontaneous carcinomas. p53 mutations were found in 58% (7/12) of spontaneous, 57% (8/14) of benzene-, and 67% (8/12) of ethylene oxide-induced carcinomas. H -ras mutations were identified in 26% (5/19) of spontaneous, 50% (7/14) of benzene-, and 33% (4/12) of ethylene oxide-induced carcinomas. When H- ras mutations were present, concurrent p53 mutations were identified in 40% (2/5) of spontaneous, 71% (5/7) of benzene-, and 75% (3/4) of ethylene oxide-induced carcinomas. Our results demonstrate that p53 and H -ras mutations are relatively common in control and chemically induced mouse mammary carcinomas although both chemicals can alter the mutational spectra and more commonly induce concurrent mutations. |
| Databáze: | OpenAIRE |
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