HYDROXYUREA INDUCES APOPTOSIS AND REGULAR DNA FRAGMENTATION IN A BURKITTS-LYMPHOMA CELL-LINE

Hydroxyurea (HU) is an S-phase-specific cytotoxic drug used in the clinical treatment of haematological malignancies. HU treatment has been shown to lead to accumulation of short DNA fragments which show direct correlation with cytotoxicity. Specific regular DNA fragmentation is a biochemical feature of apoptosis (programmed cell death) in some systems. We investigated the effect of HU on a neoplastic (Burkitt's lymphoma) cell line (BM13674) in vitro to determine the role of apoptosis in HU action. HU produced growth inhibition and cell death by apoptosis in BM13674 cells. Low dose HU (66 and 131-mu-mol/l) gave a growth inhibition effect only with no apoptosis being induced. Higher doses (0.66-13 mmol/l) induced apoptosis in a dose-dependent manner. Regular DNA fragmentation was detected by agarose gel electrophoresis of DNA and this correlated in time with the onset of apoptosis detected by light and electron microscopy. The results do not exclude the possibility that HU directly induces DNA strand breaks, which then initiate apoptosis and accompanying regular fragmentation of DNA in the apoptotic cells.