p53 Mutational status and survival of human breast cancer MCF-7 cell variants after exposure to X rays or fission neutrons
- Univ. of Maryland, Baltimore, MD (United States); and others
We assessed cytotoxicity of X rays or fission neutrons and the status of the p53 tumor suppressor gene in irradiated and unirradiated actively growing cultures of human breast cancer MCF-7 cells. One parental or wild-type (WT) and the other resistant to adriamycin (ADR{sup R}) were studied within the same experiment. We found that, relative to MCF-7 WT cells, MCF-7 ADR{sup R} cells exhibited a small but significant resistance to X rays, but not to fission neutrons. Single-strand conformation polymorphism analysis followed by DNA sequencing and immunohistochemical staining with a p53 protein-specific antibody performed on pooled polyclonal or monoclonal populations of MCF-7 WT or ADR{sup R} cells confirmed that wild-type cells have two normal copies of the p53 gene. We discovered p53 loss of heterozygosity and a point mutation in the remaining allele of the p53 gene in adriamycin-resistant cells. This mutation is a splice acceptor site change on the upstream border of exon 5 and results in p53 protein overexpression. No new p53 mutations were observed in MCF-7 WT or ADR{sup R} cells surviving either X or fission-neutron irradiations. Our results suggest that the mutant p53 allele affects cytotoxic outcomes of DNA damage from X rays but not from neutrons. 64 refs., 5 figs., 1 tab.
- Sponsoring Organization:
- USDOE
- OSTI ID:
- 90894
- Journal Information:
- Radiation Research, Journal Name: Radiation Research Journal Issue: 3 Vol. 142; ISSN 0033-7587; ISSN RAREAE
- Country of Publication:
- United States
- Language:
- English
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