The thermal response and development of thermotolerance of the bone marrow stromal progenitor CFU-F

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Abstract

The effect of hyperthermia on the murine bone marrow stromal progenitor (fibroblast colony-forming unit, CFU-F) was evaluated and its ability to develop thermotolerance demonstrated. CFU-F were obtained from nucleated marrow of Balb/c mice and heated in vitro in alpha minimum essential medium plus 15% fetal bovine serum. Thermotolerance development was tested two ways. 1) The development of thermotolerance during prolonged hyperthermia was observed with a 'step-up' heating protocol (i.e., cells were incubated at 41°C and at regular intervals challenged with 15 min at 44°C). 2) The development of thermotolerance at 37°C after a short exposure to a high temperature (≥43°C) was observed with a split treatment protocol that consisted of two 15-min treatments of 44°C separated with time at 37°C. The inverse of the slopes of the hyperthermia dose-response relationships (D(o) ± SE) for CFU-F were 118 ± 14, 53 ± 7, 23 ± 0.6, 11 ± 0.3, 7 ± 0.3, and 5 ± 0.5 min for exposures of 41.5°, 42°, 42.5°, 43°, 43.5°, and 44°C, respectively. The plot of the slopes of the heat 'dose-response' relationships versus the inverse of the absolute temperature (Arrhenius plot) yields a change in slope at approximately 43°C, and the inactivation enthalpies (slopes above and below the inflection point at 43°C) were 606 ± 100 kJ/mol (145 ± 24 kcal/mol) and 1372 ± 29 kJ/mol (328 ± 7 kcal/mol) above and below 43°C, respectively. The maximum thermotolerance ratio (TTR, surviving fraction after maximum thermotolerance development to surviving fraction of normotolerant CFU-F) at 37°C after an acute thermal exposure to 15 min at 44°C occurred after 12 h, with a half time of 60 min and a TTR of 41. The maximum TTR during prolonged hyperthermia at 41°C was 2.4 by approximately 50 min. These results show that CFU-F are as sensitive as committed hematopoietic precursors (e.g., granulocyte-macrophage colony-forming units, CFU-GM) to hyperthermia over a wide range of thermal exposures and are capable of thermotolerance development during prolonged hyperthermic exposures and at 37°C after short exposures. We conclude that at least one of the stromal elements of normal marrow may be compromised during whole-body or regional clinical hyperthermia protocols.

Original languageEnglish (US)
Pages (from-to)1096-1100
Number of pages5
JournalExperimental Hematology
Volume19
Issue number11
Publication statusPublished - Nov 27 1991

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Keywords

  • Bone marrow stroma
  • CFU-F
  • Hyperthermia
  • Thermotolerance

ASJC Scopus subject areas

  • Molecular Biology
  • Hematology
  • Genetics
  • Cell Biology
  • Cancer Research

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