p53 mutations increase resistance to ionizing radiation

Journal Article · Tue Jun 15 00:00:00 EDT 1993 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.90.12.5742· OSTI ID:6246601

Lee, J M ^[1]; Bernstein, A ^[2]

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1. Mount Sinai Hospital, Toronto, Ontario (Canada)
2. Mount Sinai Hospital, Toronto, Ontario (Canada) Univ. of Toronto, Ontario (Canada)

Mouse and human tumors of diverse origin frequently have somatically acquired mutations or rearrangements of the p53 gene, or they have lost one or both copies of the gene. Although wild-type p53 protein is believed to function as a tumor-suppressor gene, it is as yet unclear how p53 mutations lead to neoplastic development. Wild-type p53 has been postulated to play a role in DNA repair, suggesting that expression of mutant forms of p53 might alter cellular resistance to the DNA damage caused by [gamma] radiation. Moreover, p53 is thought to function as a cell cycle checkpoint after irradiation, also suggesting that mutant p53 might change the cellular proliferative response to radiation. The authors have used transgenic mice expressing one of two mutant alleles of p53 to test this prediction. Their results show that expression of both mutant variants of the mouse p53 gene significantly increases the cellular resistance of a variety of hematopoietic cell lineages to [gamma] radiation. These observations provide direct evidence that p53 mutations affect the cellular response to DNA damage, either by increasing DNA repair processes or, possibly, by increasing cellular tolerance to DNA damage. The association of p53 mutations with increased radioresistance suggests possible mechanisms through which alterations in the p53 gene might lead to oncogenic transformation. 53 refs., 5 figs.

• OSTI ID: 6246601
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Vol. 90:12; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
DNA REPAIR
GENETIC RADIATION EFFECTS
BIOLOGICAL ADAPTATION
GAMMA RADIATION
MUTATIONS
NEOPLASMS
TRANSGENIC MICE
ANIMALS
BIOLOGICAL EFFECTS
BIOLOGICAL RADIATION EFFECTS
BIOLOGICAL RECOVERY
BIOLOGICAL REPAIR
DISEASES
ELECTROMAGNETIC RADIATION
GENETIC EFFECTS
IONIZING RADIATIONS
MAMMALS
MICE
RADIATION EFFECTS
RADIATIONS
REPAIR
RODENTS
TRANSGENIC ANIMALS
VERTEBRATES
560120* - Radiation Effects on Biochemicals
Cells
& Tissue Culture