Biol. Pharm. Bull. 28(10) 1954—1957 (2005)

riety of human malignancies. CDDP is a well-known DNAdamaging agent, and it is currently thought that DNA platination is an essential first step in its cytotoxic activity. Recent evidence has shown that apoptosis is a marker of tumor cells that have been exposed to CDDP. In addition, CDDP has been reported to induce apoptosis at higher concentrations than the clinical dose. The CDDP is a type of drug whose effects depends on the area under the concentration–time curve (AUC ), which means that continuous exposure low concentrations of the drug have the same effect as a single short-term exposure at a high concentration. Continuous infusion or multiple administrations of low-dose CDDP is an excellent regimen for cancer patients. For this reason, sustained release formulations of CDDP or CDDP derivatives have been developed. However, it has not been clear whether continuous exposure with low-dose CDDP can induce apoptosis as effectively as a single high-dose exposure CDDP. We therefore compared the ability of CDDP to induce apoptosis when delivered as a single high-dose exposure or as multiple low-dose exposures. In these studies, the induction of apoptosis was assessed by measuring caspase-3 activity, DNA fragmentation, and the percent of cells in the subG1 phase.