ABSTRACT
This chapter focuses on the induction of apoptosis by nucleoside analogs both in vitro and in vivo, and discusses the roles of bcl-2, p53, and other regulatory molecules in drug-induced apoptosis. In vitro studies with leukemia cells freshly obtained from patients prior to and after chemotherapy have provided important insights into the biochemical and molecular events during nucleoside analog-induced apoptosis. Apoptosis is a key pathway by which nucleoside analogs exert their cytotoxic action against cancer cells. Although this class of drugs acts at multiple cellular targets, the incorporation of the analogs into cellular DNA is a critical event in triggering apoptotic response. The chapter discusses the relationship between nucleosomal and high molecular weight DNA fragmentation and their roles in the drug-induced apoptotic process. DNA of leukemia cells from nine patients with chronic lymphocytic leukemia receiving fludarabine-based therapy was analyzed by pulsed field gel electrophoresis.
