Induction of thermotolerance and heat-shock protein synthesis during nutritional deprivation.
Under various conditions of heating, H35 cells were submitted to acute nutritional deprivation by omitting a number of substrates (L15D medium). At 37 degrees C cell death starts after a lag-period of 3-5 h. During hypothermia cell death is delayed, whereas during hyperthermia it is accelerated especially as a result of thermosensitization. In L15D the ATP level decreases approximately 3 times faster in combination with hyperthermia than at 37 degrees C. In non-thermotolerant cells thermosensization is very high at 41 degrees C and decreases with increasing temperature; in thermotolerant cells it is comparatively decreased at 41 degrees C and increased at 42.5 degrees C and above. In response to a heat shock of 30 min at 42.5 degrees C only 10% of the cell population expresses acute thermotolerance after incubation at 37 degrees C in L15D as compared to nearly 100% in complete medium (L15C). Chronic development of thermotolerance appears to be even more repressed in the presence of L15D, which partly explains the high thermosensitization at 41 degrees C. Changes in the rate of protein synthesis for combinations of nutritional deprivation and hyperthermia show a correlation with the cell survival data. Development of acute thermotolerance in L15D is accompanied by an increase in heat-shock protein synthesis relative to total protein. At 41 degrees C in L15D no heat-shock protein induction could be detected. Of the omitted substrates only glutamine can effectively abolish thermosensitization and the effects of L15D on protein and heat-shock protein synthesis depending on the condition of the cells, thermotolerant or non-thermotolerant, and to a different extent for the various proteins considered.
van Rijn
J
J
Department of Radiation Oncology, Free University Hospital, Amsterdam, The Netherlands.
van den Berg
J
J
van Aken
H
H
van Wijk
R
R
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003470:Culture Media; D005973:Glutamine / Q000494:pharmacology; D006360:Heat-Shock Proteins / Q000096:biosynthesis*; D006358:Hot Temperature; D007700:Kinetics; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D003470:Culture Media; D006360:Heat-Shock Proteins; D005973:Glutamine; D000255:Adenosine Triphosphate