Effect of etanidazole on absolute sensitivity and increased radioresistance in hypoxic cells at low doses

Kirsten A. Skov, Cameron J. Koch, Brian Marples

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

It has been known for some time that oxygen and certain electron affinic radiosensitizers exhibit less effective enhancement of cell kill at low clinically relevant X‐ray doses, a behavior which has still not been adequately explained. This is further complicated by more recent findings that at low concentrations of nitroimidazoles there are anomalous results on hypoxic low dose radiosensitization. In the low dose range below 1 Gy, where survival is high, we have reexamined radiosensitization of hypoxic hamster cells by etanidazole at various concentrations (200–2,000 μM) using automated microscopic localization of cells to obtain more precise measurements of survival. As previously observed, etanidazole at low concentrations (200 μM) was found to be more effective at low (∼1 Gy, survival ∼80%) rather than high (survival ∼2%) X‐ray doses. When plotted as absolute sensitivity, data for high concentrations of etanidazole (> 1,000 μM) fall in one area of the D80 −1 vs. D2 −1 plot, whereas concentrations below 1,000 μM might be suggested to behave “differently,” and several explanations are suggested. One of these involves a structure of the survival curve which has been suggested to reflect induced repair. This structure is modified at the higher concentration of etanidazole, but there is little effect at 200 μM. An alternate proposal considers accessibility of DNA to drug, or type of lesions affected as possible explanations for the apparent differential sensitization by etanidazole at high and low X‐ray doses. In summary, a clinically relevant concentration of etanidazole provides relatively good radiosensitization at low, clinically relevant radiation doses; thus hypoxic sensitizers may affect survival in those cell lines which have a large survival curve shoulder since the extent of the shoulder is purported to reflect the degree of induced radioresistance. © Wiley‐Liss, Inc.

Original languageEnglish (US)
Pages (from-to)164-170
Number of pages7
JournalRadiation Oncology Investigations
Volume2
Issue number4
DOIs
StatePublished - Jan 1 1994
Externally publishedYes

Keywords

  • absolute sensitivity
  • hypersensitivity
  • nitroimidazoles
  • radioresistance
  • radiosensitizers

ASJC Scopus subject areas

  • Radiation
  • Radiological and Ultrasound Technology
  • Oncology
  • Radiology Nuclear Medicine and imaging

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