Hyperthermic sensitivity and cholesterol levels of mammalian cell lines in culture.

In this study, we asked whether cholesterol contents were specifically correlated with cellular sensitivity to hyperthermia. To examine this possibility, we employed two isogenic mammalian cell lines, Chinese hamster V79 cell line and its amphotericin B-resistant (AMBr) cell line. AMBr cells had a decreased content of membrane sterols in comparison with V79 cells. Clonogenic assays showed that AMBr cells were more sensitive to hyperthermic treatment at 45 degrees C than V79 cells. Cholesterol contents were increased in AMBr cells by exposure to liposomes containing 1:1 lecithin-cholesterol, and the sterol level was comparable to that of V79 cells. In comparison with untreated AMBr cells, AMBr cells were more resistant to hyperthermia at 45 degrees C when incubated with liposomes containing cholesterol. Treatment of V79 cells with oxygenated sterol, a potent inhibitor of endogeneous sterol synthesis, sensitized the hyperthermic cytotoxicity. Our present data present the hypothesis that cellular cholesterol contents are closely correlated with cellular heat toxicity.