SENSITIZATION TO HYPERTHERMIA BY 3,3'-DIPENTYLOXACARBOCYANINE IODIDE - A POSITIVE CORRELATION WITH DNA DAMAGE AND NEGATIVE CORRELATIONS WITH ALTERED CELL MORPHOLOGY, OXYGEN-CONSUMPTION INHIBITION, AND REDUCED ATP LEVELS

The cyanine dye 3,3'-dipentyloxacarbocyanine iodide (DiOC5(3)) (concentrations of 0.5-mu-g/ml to 5.0-mu-g/ml) was shown to be a potent sensitizer of Chinese hamster ovary (CHO) cells to hyperthermic cell killing at 43.0-degrees-C or 45.5-degrees-C, while exhibiting no cytotoxicity at 37.0-degrees-C. Sensitization to hyperthermic cell killing was accompanied by an increase in damage to the DNA, as measured by DNA unwinding. The increased DNA damage correlated qualitatively with the enhanced heat killing induced by DiOC5(3). This correlation was better in cells heated at 43.0-degrees-C than in those heated at 45.5-degrees-C. DiOC5(3) is known to affect other cellular functions. It inhibits electron transport, uncouples oxidative phosphorylation, and inhibits calcium ATPases. The effects of DiOC5(3) on oxygen consumption and ATP content were therefore measured at 37.0-degrees-C and at hyperthermic temperatures. The results demonstrated that inhibition of oxygen consumption and reduction of cellular ATP levels played no role in inducing heat sensitization in DiOC5(3)-treated cells, or in causing cell death in cells treated with heat alone.