Differential sensitivity to hyperthermia of mouse normal haemopoietic stem cells related to proliferation activity and organ source

Abstract

Thermosensitivity of haemopoietic stem cells was studied in relation to the organ source and the proliferative state of the cells. Heat treatment was carried out at 41, 42, 43, 44 and 45°C until about 1 per cent survival was reached. Treatments at 42°C and below appear to be critical in revealing thermosensitivity differences between haemopoietic stem cells, characterized by the time T_O at a given temperature to induce a lethal event. At these temperatures, foetal liver CFU-S (about 35 per cent in S phase) were more thermosensitive than steady-state bone marrow and spleen CFU-S (less than 10 per cent in S). We consider that these thermosensitivity differences cannot be attributed exclusively to differences in proliferation rates of the CFU-S, since exponentially-proliferating marrow CFU-S (48 per cent in S) does not significantly differ in sensitivity compared with steady-state CFU-S, while regenerating spleen CFU-S does (34 per cent in S). An Arrhenius analysis of heat survival curves of the different CFU-S allowed us to estimate only one activation energy (E_a) in the inactivation process of foetal liver and regenerating spleen CFU-S, and two E_a in the case of steady-state marrow and spleen CFU-S and regenerating marrow CFU-S.

Key Words:

• hyperthermia
• haemopoietic stem cells
• proliferative state
• organ sources.