Differential enhancement of cytotoxicity by combination of the carcinostatic agent benzaldehyde and hyperthermia in simian virus 40-transformed and normal cell lines.

The effect of the carcinostatic drug benzaldehyde (BA) on hyperthermia-induced cytotoxicity was studied in various types of cultured mammalian cell lines by colony formation assay. The treatment of HeLa cells with nontoxic doses of BA (1 to 4 mM) at 42 and 43 degrees for up to 3 hr induced enhancement of cell killing. BA-induced enhancement of hyperthermic cell killing was much greater in SV40-transformed rat fibroblast cells than in the untransformed cell line. This BA-induced differential enhancement of hyperthermic cell killing increased as the time and dose of BA treatment were increased at elevated temperatures. For example, BA (2 mM) treatment for 4 hr at 42 degrees decreased the survival of transformed cells to 2 X 10(-4), but decreased the survival of untransformed cells to only 0.1. Furthermore, BA (4 mM) treatment for 2 hr at 42 degrees reduced the survival of transformed cells to less than 10(-5), but reduced the survival of untransformed cells to 5 X 10(-2). Differential enhancement of hyperthermic cytotoxicity by BA was also evident between normal human diploid fibroblast W138 cells and its SV40-transformed cell line, although the magnitude of the enhancement was less than that observed with rat cell lines. The determination of BA remaining in the medium after incubation with transformed and untransformed rat cells at 37, 42, and 43 degrees suggested that greater amounts of BA reacted with or were consumed by transformed cells irrespective of temperature.