A comparison of the heat and radiation sensitivity of rodent and human derived cells cultured in vitro

Abstract

A human lung and breast carcinoma cell line of epithelial origin (A-549 and MCF-7) were compared with a rodent fibroblast line (V-79) for their sensitivity to killing by X rays and heat, in addition, a correlation was sought between loss of endogenous thiols and thermosensitivity. Endogenous cellular thiols play a major role in many protective, enzymatic and synthetic processes in mammalian cells. Glutathione, a key non-protein thiol, not only protects against radiation and peroxide-induced damage, but is also a primary intracellular reductant. Thiol depletion was achieved using two agents that work by totally different mechanisms-one a substrate for glutathione-S-transferase (Diethylmaleate) and the other an inhibitor of a key enzyme in the gamma-glutamyl cycle (Buthionine-SR-Sulfoximine). The results of this study demonstrated that thiol depletion by DEM to 50% of the control values had no effect on the response of hamster cells to acute (45°C) or chronic (42.5°C) hyperthermia. Substantial potentiation of heat damage, however, was seen at thiol levels below 10% at 42.5°C. Thiol depletion by BSO to levels of 25% of the control values had no sensitizing effect on the heat sensitivity of hamster or human lung carcinoma cells at 45°C. For any given heat exposure, the human cells were markedly more resistant to killing than the hamster cells, however, they were more radiosensitive than the V79, line when exposed to 300 kVp X rays (Do's of 1.65 vs. 2.52 Gy). The results of this study indicate that thiols do not play a critical role in mammalian cell thermosensitivity at 45°C and indicate that the use of human carcinoma cell lines may better predict heat inactivation in human cells in vivo.