ENHANCED INHIBITORY EFFECTS OF HYPERTHERMIA COMBINED WITH ASCORBIC-ACID ON DNA-SYNTHESIS IN EHRLICH ASCITES TUMOR-CELLS GROWN AT A LOW CELL-DENSITY

Effects of hyperthermia and cell densities on inhibitory activity of a scorbic acid on DNA synthesis in Ehrlich ascites tumor cells were stud ied. When cells at a low density of 5 x 10(3)/ml were treated with 75 mu M ascorbic acid for 1 h, DNA synthesis was inhibited after treatmen t at 37 degrees C and the inhibition was significantly enhanced at 42 degrees C. At a cell density as high as 1 x 10(5)/ml, however, inhibit ion did not occur at 37 degrees C or 42 degrees C. In contrast, dehydr oascorbic acid was inactive even at a low cell density under similar c onditions. Inhibitory effects of ascorbic acid on DNA synthesis were a lso markedly enhanced by treatment at 40 degrees C. DNA synthesis was not inhibited in the absence of the drug. Furthermore, mice transplant ed with cells treated with a combination of 75 mu M ascorbic acid and hyperthermia at 42 degrees C, considerably prolonged their survival ti me in comparison with untreated cells. Addition of ascorbic acid to hy perthermia is suggested to be an advantageous treatment for cancer.