Lassmann G, Liermann B
Central Institute of Molecular Biology, Academy of Sciences of GDR, Berlin-Buch.
Free Radic Biol Med. 1989;6(3):241-4. doi: 10.1016/0891-5849(89)90050-6.
Hydroxyurea (HU) is a clinically applied antineoplastic drug, which quenches tyrosine radicals in the active site of ribonucleotide reductase (RR) and inhibits DNA synthesis in proliferating cells. Under oxidizing conditions (Cu2+ or H2O2) long-lived radicals from HU have been found by ESR. The structure of HU radicals was established to be: (formula; see text). The kinetics of formation and decay of HU radicals after reaction of HU with H2O2 is complex; it exhibits a lag-phase, a maximum, and a decay, all depending on the concentration of HU. Biological consequences of HU radicals for the inhibition of RR as well as their role in cytotoxic events during chemotherapy of cancer are discussed.
羟基脲（HU）是一种临床应用的抗肿瘤药物，它能淬灭核糖核苷酸还原酶（RR）活性位点的酪氨酸自由基，并抑制增殖细胞中的DNA合成。在氧化条件下（Cu2+或H2O2），通过电子自旋共振（ESR）发现了来自HU的长寿命自由基。已确定HU自由基的结构为：（分子式；见正文）。HU与H2O2反应后HU自由基形成和衰减的动力学很复杂；它呈现出一个延迟期、一个最大值和一个衰减期，所有这些都取决于HU的浓度。讨论了HU自由基对RR抑制的生物学后果以及它们在癌症化疗期间细胞毒性事件中的作用。
