Alterations in the K-ras and p53 genes in rat lung tumors
| العنوان: | Alterations in the K-ras and p53 genes in rat lung tumors |
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| المؤلفون: | D. S. Swafford, Kristen J. Nikula, Gregory Kelly, Charles E. Mitchell, Marshall W. Anderson, Gregory L. Finch, Fletcher F. Hahn, Steven A. Belinsky |
| المصدر: | Environmental Health Perspectives |
| بيانات النشر: | Environmental Health Perspectives, 1997. |
| سنة النشر: | 1997 |
| مصطلحات موضوعية: | Mutation, Lung Neoplasms, Transition (genetics), DNA damage, Health, Toxicology and Mutagenesis, Public Health, Environmental and Occupational Health, Nuclear Proteins, Proto-Oncogene Proteins c-mdm2, Single-strand conformation polymorphism, Biology, Gene mutation, Genes, p53, medicine.disease_cause, Molecular biology, Rats, Genes, ras, Proto-Oncogene Proteins, medicine, Animals, Mutation frequency, Protein stabilization, Gene, Research Article, DNA Damage |
| الوصف: | Activation of the K-ras protooncogene and inactivation of the p53 tumor suppressor gene are events common to many types of human cancers. Molecular epidemiology studies have associated mutational profiles in these genes with specific exposures. The purpose of this paper is to review investigations that have examined the role of the K-ras and p53 genes in lung tumors induced in the F344 rat by mutagenic and nonmutagenic exposures. Mutation profiles within the K-ras and p53 genes, if present in rat lung tumors, would help to define some of the molecular mechanisms underlying cancer induction by various environmental agents. Pulmonary adenocarcinomas or squamous cell carcinomas were induced by tetranitromethane (TNM), 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK), beryllium metal, plutonium-239, X-ray, diesel exhaust, or carbon black. These agents were chosen because the tumors they produced could arise via different types of DNA damage. Mutation of the K-ras gene was determined by approaches that included DNA transfection, direct sequencing, mismatch hybridization, and restriction fragment length polymorphism analysis. The frequency for mutation of the K-ras gene was exposure dependent. Only two agents, TNM and plutonium, led to mutation frequencies of > 10%. In both cases, the transition mutations formed could have been derived from deamination of cytosine. The identification of non-ras transforming genes in rat lung tumors induced by mutagenic and nonmutagenic exposures such as NNK and beryllium would help define some of the mechanisms underlying cancer induction by different types of DNA damage. Alteration in the p53 gene was assessed by immunohistochemical analysis for p53 protein and single-strand conformation polymorphism (SSCP) analysis of exons 4 to 9. None of the 93 adenocarcinomas examined was immunoreactive toward the anti-p53 antibody CM1. In contrast, 14 to 71 squamous cell carcinomas exhibited nuclear p53 immunoreactivity with no correlation to type of exposure. However, SSCP analysis only detected mutations in 2 of 14 squamous cell tumors that were immunoreactive, suggesting that protein stabilization did not stem from mutations within the p53 gene. Thus, the p53 gene does not appear to be involved in the genesis of most rat lung tumors. Images Figure 1. Figure 2. |
| تدمد: | 1552-9924 0091-6765 |
| DOI: | 10.1289/ehp.97105s4901 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::933a390e410adf7540106433ffc009d0 https://doi.org/10.1289/ehp.97105s4901 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....933a390e410adf7540106433ffc009d0 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15529924 00916765 |
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| DOI: | 10.1289/ehp.97105s4901 |