Effect of pH, oxygenation, and temperature on the cytotoxicity and radiosensitization by etanidazole

Beverly A. Teicher, Terence S. Herman, Sylvia A. Holden

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

The effect of etanidazole was examined in vitro and in vivo in the FSaIIC tumor system. At pH 7.40 and 37°C, etanidazole at 5-500 μM for 1 hr was minimally cytotoxic. At 42°C and 43°C, however, the cytotoxicity of etanidazole increased. Etanidazole was more cytotoxic at pH 6.45 and 37° than at pH 7.40 by about I log. Increasing the temperature to 42°C or 43°C at pH 6.45 during drug exposure, however, caused little increase in drug killing above the lethality of hyperthermia. When the radiosensitizing abilities of etanidazole were tested in vitro, there was a radiation dose modifying factor of 2.40 at pH 7.40, but only 1.70 at pH 6.45. In vivo, etanidazole (1 g/kg) produced a radiation dose modifying factor of 1.47, whereas 43°C for 30 min produced a radiation dose modifying factor of 1.38. The combination resulted in a radiation dose modifying factor of 2.29. When the cytotoxicities of hyperthermia (43°C × 30 min), etanidazole (500 mg/kg or 1 mg/kg), and radiation (10 Gy) combinations were assayed by Hoechst 33342 dye selected tumor subpopulations, 43°C × 30 min increased the killing of irradiated dim cells by ∼9.2-fold but by only 2.9-fold in bright cells. Etanidazole (1 g/kg) increased radiation killing of bright cells by about 3-fold and dim cells by about 4.3-fold. The combination of hyperthermia and etanidazole increased the killing of both dim and bright cells exposed to radiation by ∼10-fold versus 10 Gy alone.

Original languageEnglish (US)
Pages (from-to)723-731
Number of pages9
JournalInternational journal of radiation oncology, biology, physics
Volume20
Issue number4
DOIs
StatePublished - Apr 1991
Externally publishedYes

Keywords

  • Combined modalities
  • Etanidazole
  • Hyperthermia
  • Hypoxia
  • pH

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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