Evidence for the involvement of DNA-dependent protein kinase in the phenomena of low dose hyper-radiosensitivity and increased radioresistance

B. Marples, N. E. Cann, C. R. Mitchell, P. J. Johnston, M. C. Joiner

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Purpose: To investigate the role of DNA-dependent protein kinase (DNA-PK) in the phenomena of low dose hyper-radiosensitivity (HRS) and increased radioresistance (IRR) using the genetically related M059 cell lines of disparate PRKDC status. Materials and methods: Clonogenic survival was measured for the three cell lines following low doses of X-irradiation using a flow-activated cell sorting (FACS) plating technique. The presence of PRKDC, G22p1 and Xrcc5 proteins was determined by Western blotting and a kinase assay used to measure DNA-PK complex activity. Results: The survival responses for the three cell lines over the 0-0.3 Gy dose range were comparable, but differences in radiosensitivity were evident at doses >0.4 Gy. M059K and M059J/Fusl cells (both PRKDC competent) exhibited marked HRS/IRR responses, albeit to different extents. M059J cells (PRKDC incompetent) were extremely radiosensitive exhibiting a linear survival curve with no evidence of IRR. The presence of IRR was coincident with the presence of PRKDC protein and functional DNA-PK activity. Conclusions: HRS is a response that is independent of DNA-PK activity. In contrast, IRR showed a dependence on the presence of PRKDC protein and functional DNA-PK activity. These data support a role for DNA-PK activity in the IRR response.

Original languageEnglish (US)
Pages (from-to)1139-1147
Number of pages9
JournalInternational Journal of Radiation Biology
Volume78
Issue number12
DOIs
StatePublished - Dec 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging

Fingerprint Dive into the research topics of 'Evidence for the involvement of DNA-dependent protein kinase in the phenomena of low dose hyper-radiosensitivity and increased radioresistance'. Together they form a unique fingerprint.

  • Cite this