The development and magnitude of thermotolerance during chronic hyperthermia in murine bone marrow granulocyte-macrophage progenitors: I

M. D. O'Hara, J. W. Boyer, C. Lin, D. B. Leeper

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Abstract

Murine bone marrow granulocyte-macrophage progenitors (CFU-GM) are capable of developing thermotolerance during exposure to temperatures <42.5°C. Bone marrow from the tibia and femora was heated to 40-42°C (i.e. chronic hyperthermia), and challenged immediately with 15 min at 44°C at regular intervals during treatment (step-up heating). CFU-GM were heated and cultured in McCoy's 5A medium + 15% FBS (fetal bovine serum) and lung-conditioned medium (source of colony stimulating factor) in semisolid agar. The kinetics of thermotolerance development and decay, and the magnitude of the thermotolerance during chronic heating with temperatures of 40-41.5°C were similar. Survival increased rapidly to a maxima by approximately 120 min of hyperthermia (temperatures of 40-41.5°C) and thereafter decreased with a slope similar to the controls. Normalization for cell killing by chronic hyperthermia that occurred during 'step-up' heating permitted analysis of thermotolerance in the surviving cells. The surviving fraction after 15 min at 44°C, during incubation at 40, 41 and 41.5°C increased from 0.13 to maxima of 0.56 ± 0.04, 0.71 ± 0.03 and 0.82 ± 0.03 respectively, by 150 min and did not decrease for up to 480 min during chronic hyperthermia. The surviving fraction after 15 min at 44°C during incubation at 42°C increased more slowly than during incubations at 40-41.5°C. The survival of thermotolerant cells after exposure to 15 min at 44°C during 42°C chronic hyperthermia was maximal at 0.87 ± 0.08 by 120 min and then decreased after approximately 150 min of exposure to 42°C. The thermotolerance ratios (TTR's) were 4.0, 5.4, 6.7 and 6.9 for temperatures of 40, 41, 41.5 and 42°C respectively. The results suggest that chronic hyperthermia temperatures (i.e. 40-42°C) induce rapid thermotolerance development in CFU-GM during the thermal exposure and protect this normal marrow progenitor during whole body hyperthermia or ex vivo purging of leukaemic cells.

Original languageEnglish (US)
Pages (from-to)87-95
Number of pages9
JournalInternational Journal of Hyperthermia
Volume12
Issue number1
DOIs
Publication statusPublished - Jan 1 1996

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Keywords

  • CFU-GM
  • Thermotolerance
  • Whole body hyperthermia

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)
  • Cancer Research

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