p53 Mutational status and survival of human breast cancer MCF-7 cell variants after exposure to X rays or fission neutrons

E. K. Balcer-Kubiczek, J. Yin, K. Lin, G. H. Harrison, J. M. Abraham, S. J. Meltzer

Research output: Contribution to journalArticlepeer-review

Abstract

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(R)) were studied within the same experiment. We found that, relative to MCF-7 WT cells, MCF-7 ADR(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(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(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.

Original languageEnglish (US)
Pages (from-to)256-262
Number of pages7
JournalRadiation research
Volume142
Issue number3
DOIs
StatePublished - 1995
Externally publishedYes

ASJC Scopus subject areas

  • Biophysics
  • Radiation
  • Radiology Nuclear Medicine and imaging

Fingerprint Dive into the research topics of 'p53 Mutational status and survival of human breast cancer MCF-7 cell variants after exposure to X rays or fission neutrons'. Together they form a unique fingerprint.

Cite this