Gene alterations in radiation-induced F344 rat lung tumors
Technical Report
·
OSTI ID:54816
The p53 tumor suppressor gene is frequently altered in all major histopathologic types of human lung tumors. Reported p53 mutations include base substitutions, allelic loss, rearrangements, and deletions. Point mutations resulting in base substitutions are clustered within a highly conserved region of the gene encoding exons 508, and mutations in this region substantially extend the half-life of the p53 protein. In addition to its prominent importance in lung carcinogenesis, the p53 gene plays a critical role in the cellular response to genetic damage caused by radiation. Specifically, the protein product of p53 induces a pause or block at the G{sub 1} to S boundary of the cell cycle following radiation-caused DNA damage. This G{sub 1} block may allow the cell time to repair the damaged DNA prior to replication. Cells lacking a functional p53 protein fail to pause for repair and consequently accumulate mutations in the genome at an accelerated rate. p53 has also been implicated as a controlling factor in apoptosis or in programmed cell death induced by DNA-damaging agents, such as ionizing radiation. The p53 gene is mutated in approximately 50% of squamous cell carcinomas from uranium miners who inhaled high doses of radon daughters. The purpose of the present study was to determine if a similar percentage of squamous cell carcinomas with p53 mutations developed in the lungs of rats exposed to aerosols of {sup 239}PuO{sub 2}.
- Research Organization:
- Lovelace Biomedical and Environmental Research Inst., Albuquerque, NM (United States). Inhalation Toxicology Research Inst.
- DOE Contract Number:
- AC04-76EV01013
- OSTI ID:
- 54816
- Report Number(s):
- ITRI--144; ON: DE95007526
- Country of Publication:
- United States
- Language:
- English
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