Division-associated and division-independent hyperthermic cell death: Comparison with other cytotoxic agents

Abstract

We have heated Chinese hamster ovary (CHO) cells in G₁ phase, and followed them by microscopic observation for 8 days. Non-clonogenic cells were monitored with regard to when they died, and whether death was preceded by cell division. Such cells underwent either a division-independent or division-associated mode of death. At high survival levels most cells died a division-associated death, while at low survival levels division-independent death predominated. Mouse 10T1/2 cells died primarily according to the division-independent mode, regardless of survival level. These data are consistent with two distinct targets for the thermal killing of G₁ cells, one of which involves the cell's ability to divide properly. The heat-induced division delay was similar for both clonogenic and non-clonogenic cells, suggesting that cell death was not due to lengthened cell cycle times. Hydrogen peroxide caused more division-independent death than heat, at isosurvival. The mode of death following cis-platinum treatment was largely division-associated, regardless of survival level. The combination of heat and cis-platinum caused synergistic killing that was due to a potentiation of cis-platinum killing by heat, since the pattern of death was clearly similar to that caused by cis-platinum alone.

Key Words:

• Hyperthermia
• cis-platinum
• hydrogen peroxide
• multinucleation