Mechanism of radiosensitization by hyperthermia (≥43°C) as derived from studies with DNA repair defective mutant cell lines

H. H. Kampinga, Joseph Dynlacht, E. Dikomey

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

All biochemical and cytogenetic data on radiosensitization by heat treatment at and above 43°C indicate that inhibition of DNA repair plays a central role. There are several DNA repair pathways involved in restoration of damage after ionising irradiation and the kinetics of all of them are affected by heat shock. This, however, does not imply that the inhibition of each of these pathways is relevant to the effect of heat on cellular radiosensitivity. The current review evaluates the available data on heat radiosensitization in mutant or knockout cell lines defective in various DNA repair proteins and/or pathways. The data show that thermal inhibition of the non-homologous end-joining pathway (NHEJ) plays no role in heat radiosensitization. Furthermore, limited data suggest that the homologous recombination pathway may also not be a major heat target. By deduction, it is suggested that inhibition of base damage repair (BER) could be the crucial step in radiosensitization by heat. While a lack of mutant cell lines and redundancy of the BER pathway have hampered efforts toward a conclusive study, biochemical and correlative evidence support this hypothesis.

Original languageEnglish
Pages (from-to)131-139
Number of pages9
JournalInternational Journal of Hyperthermia
Volume20
Issue number2
DOIs
StatePublished - Mar 2004

Fingerprint

DNA Repair
Fever
Hot Temperature
Cell Line
Radiation Tolerance
Homologous Recombination
Cytogenetics
Shock
Proteins

Keywords

  • BER
  • DNA repair
  • DNA repair mutant
  • HR
  • Hyperthermia
  • NHEJ
  • Radiation

ASJC Scopus subject areas

  • Cancer Research
  • Radiological and Ultrasound Technology

Cite this

Mechanism of radiosensitization by hyperthermia (≥43°C) as derived from studies with DNA repair defective mutant cell lines. / Kampinga, H. H.; Dynlacht, Joseph; Dikomey, E.

In: International Journal of Hyperthermia, Vol. 20, No. 2, 03.2004, p. 131-139.

Research output: Contribution to journalArticle

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