Hyperthermia, intracellular free calcium and calcium ionophores.
It is shown that heat-induced increase of intracellular calcium does not correlate with hyperthermic cell killing. Six different cell lines were investigated; in four (EAT, HeLa S3, L5178Y-R and L5178Y-S) heat treatments killing 90% of the cells did not affect the levels of intracellular free calcium ([Ca2+]i). In one cell line (3T3) a heat-induced increase in [Ca2+]i was observed. LM cells showed a heat-induced increase of the ratio of the fluorescent signals, but this may be explained by Fura-2 leakage out of the cells. Calcium ionophores are used to address the question whether rises in [Ca2+]i might cause cell killing. To investigate the existence of sensitization to Ca2+ toxicity by heat, ionophore treatments are combined with hyperthermia. Both ionophores used, A23187 and ionomycin, cause cell killing corresponding with increases in [Ca2+]i at 37 degrees C in EAT cells. In HeLa S3 cells, substantial increases in [Ca2+]i due to the action of ionomycin were observed without corresponding cell killing. This indicates the presence of a threshold concentration of [Ca2+]i in HeLa S3 cells before the treatment becomes toxic. Both ionophores show synergism with hyperthermia for cell killing as well as at the level of increased [Ca2+]i. The synergistic action may be explained as thermal enhancement of calcium toxicity.
Stege
G J
GJ
Department of Radiobiology, University of Groningen, The Netherlands.
Wierenga
P K
PK
Kampinga
H H
HH
Konings
A W
AW
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D016923:Cell Death; D002460:Cell Line; D006358:Hot Temperature / Q000009:adverse effects*; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D007476:Ionophores / Q000494:pharmacology*
D007476:Ionophores; D000001:Calcimycin; D015759:Ionomycin; D002118:Calcium