Johnson C A, Forster T H, Winterford C M, Allan D J
Centre for Molecular Biotechnology, Queensland University of Technology, Brisbane, Australia.
Biochim Biophys Acta. 1992 Jul 22;1136(1):1-4. doi: 10.1016/0167-4889(92)90076-n.
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 mumol/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.
羟基脲（HU）是一种用于血液系统恶性肿瘤临床治疗的S期特异性细胞毒性药物。已证明HU治疗会导致短DNA片段的积累，这些片段与细胞毒性直接相关。特定的规则DNA片段化是某些系统中细胞凋亡（程序性细胞死亡）的生化特征。我们在体外研究了HU对一种肿瘤性（伯基特淋巴瘤）细胞系（BM13674）的作用，以确定细胞凋亡在HU作用中的作用。HU在BM13674细胞中通过细胞凋亡产生生长抑制和细胞死亡。低剂量HU（66和131μmol/L）仅产生生长抑制作用，未诱导细胞凋亡。较高剂量（0.66 - 13 mmol/L）以剂量依赖方式诱导细胞凋亡。通过DNA琼脂糖凝胶电泳检测到规则的DNA片段化，并且这与通过光学和电子显微镜检测到的细胞凋亡的开始在时间上相关。结果不排除HU直接诱导DNA链断裂的可能性，然后引发细胞凋亡以及凋亡细胞中伴随的规则DNA片段化。
