TEMPERATURE INFLUENCES BOTH CYTOTOXICITY AND DNA NICKING EFFICIENCY OF THE ANTITUMOR DISTAMYCIN ANALOG FCE24517

The number of DNA single strand breaks generated by FCE2417 increases exponentially while covalent adducts linearly accumulate at a higher r ate. Kinetics studies indicate that the rate of DNA fragmentation is t emperature-dependent. The sites of DNA strand breaks do not change in the 30-65 degrees C range. The cytotoxic potency of FCE24517 is also a ffected by temperature, since a shift up of 6 degrees C during the 4 h exposure of human colon carcinoma cells raises the cytotoxic efficien cy fivefold. These results are consistent with the hypothesis that the biological activity of this new drug relates to its electrophilic pro perties.