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

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

Research output: Contribution to journalArticle

30 Citations (Scopus)

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

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DNA-Activated Protein Kinase
Radiation Tolerance
Cell Line
Proteins
Phosphotransferases
Western Blotting

ASJC Scopus subject areas

  • Radiological and Ultrasound Technology
  • Radiology Nuclear Medicine and imaging

Cite this

Evidence for the involvement of DNA-dependent protein kinase in the phenomena of low dose hyper-radiosensitivity and increased radioresistance. / Marples, Brian; Cann, N. E.; Mitchell, C. R.; Johnston, P. J.; Joiner, M. C.

In: International Journal of Radiation Biology, Vol. 78, No. 12, 01.12.2002, p. 1139-1147.

Research output: Contribution to journalArticle

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AU - Cann, N. E.

AU - Mitchell, C. R.

AU - Johnston, P. J.

AU - Joiner, M. C.

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