Day R S
Department of Medicine, Cross Cancer Institute, Edmonton, Alb., Canada.
Mutat Res. 1993 Mar;293(3):215-23. doi: 10.1016/0921-8777(93)90072-o.
Hydroxyurea, an inhibitor of ribonucleotide reductase, blocks the repair by normal human fibroblasts of ultraviolet light-damaged adenovirus 5. A mixture of all four DNA deoxynucleosides present with hydroxyurea reversed the inhibition, an effect consistent with the target of hydroxyurea being ribonucleotide reductase. Single deoxynucleosides were differentially effective in reversing the inhibition: deoxyguanosine reversed 100% of the HU block, deoxyadenosine 70%, deoxythymidine 55%, but deoxycytidine only 3%. The results are interpreted in the context of the known pattern of stimulation and inhibition of mammalian ribonucleotide reductase by dNTP effectors. We suggest that biological data may be important to assessing the availability of substrate for the ribonucleotide reductase molecules that provide dNTPs for DNA repair.
羟基脲是一种核糖核苷酸还原酶抑制剂，可阻断正常人成纤维细胞对紫外线损伤的腺病毒5的修复。羟基脲与所有四种DNA脱氧核苷混合可逆转这种抑制作用，这一效应与羟基脲的作用靶点为核糖核苷酸还原酶一致。单一脱氧核苷在逆转抑制方面的效果存在差异：脱氧鸟苷可逆转100%的羟基脲阻断作用，脱氧腺苷为70%，脱氧胸苷为55%，但脱氧胞苷仅为3%。这些结果是在已知的dNTP效应物对哺乳动物核糖核苷酸还原酶的刺激和抑制模式的背景下进行解释的。我们认为，生物学数据对于评估为DNA修复提供dNTP的核糖核苷酸还原酶分子的底物可用性可能很重要。
