Caffeine sensitization of Chinese hamster ovary cells to heat killing

The effects of the methylxanthine, caffeine, on heat sensitization was investigated using Chinese hamster ovary (CHO) cells. Caffeine sensitized CHO cells to heat killing by reducing both the shoulder and the slope of the 44 degrees C survival curve. Heating was performed in suspension by addition of cells to preheated spinner flasks containing caffeine. Changes in intracellular free calcium levels, [Ca2+]i, were measured at 37 degrees C using the luminescent probe aequorin. Caffeine (1-5 mM) induced a transient increase in [Ca2+]i at 37 degrees C. The transient increase in [Ca2+]i was reduced 15-fold when 5 mM caffeine was added to aequorin-loaded cells suspended in Ca(2+)-free Hanks' balanced salt solution. However, 5 mM caffeine sensitized the cells to the same extent when they were suspended in either Ca(2+)-containing or Ca(2+)-free Hanks' balanced salt solution. The mechanism of heat sensitization by caffeine is still unknown.