胸苷和胸苷酸类似物对肿瘤细胞核酸合成的影响。
Effect of thymidine and thymidylate analogs on nucleic acid synthesis in tumor cells.
作者信息
Toide H, Akiyoshi H, Minato Y, Fujii S
出版信息
Gan. 1977 Apr;68(2):159-63.
Synthetic 5'-amino-5'-deoxythymidine (5'-AdThd), alpha,beta-methylenethymidine diphosphate (alpha,beta-MTDP), and alpha,beta-methylenethimidine triphosphate (alpha,beta-MTTP) were found to inhibit thymidine kinase. Using thymidine kinase extracted from FM 3A/B cells (a strain of mouse mammary gland tumor cells), the Ki values of 5'-AdThd, alpha,beta-MTDP, and alpha,beta-MTTP against thymidine were calculated to be 9.2 X 10(-5)M, 2.3 X 10(-5) M, and 1.8 X 10(-5) M, respectively. At concentrations above their Ki values alpha,beta-MTDP and alpha,beta-MTTP did not inhibit incorporation of labeled thymidine into DNA of cultured cells, whereas 5'-AdThd did. Under the same conditions all three compounds inhibited TMP incorporation. The inhibitions of thymidine and TMP incorporation were specific, since the incorporation of deoxyguanosine was scarcely inhibired by 5'-AdThd. These results suggested that the specific inhibition of thymidine and TMP incorporation was mostly due to reduction in permeability of the cells to these substrates rather than to inhibition of thymidine kinase activity.
已发现合成的5'-氨基-5'-脱氧胸苷（5'-AdThd）、α,β-亚甲基胸苷二磷酸（α,β-MTDP）和α,β-亚甲基胸苷三磷酸（α,β-MTTP）可抑制胸苷激酶。使用从FM 3A/B细胞（一种小鼠乳腺肿瘤细胞系）中提取的胸苷激酶，计算出5'-AdThd、α,β-MTDP和α,β-MTTP对胸苷的Ki值分别为9.2×10⁻⁵M、2.3×10⁻⁵M和1.8×10⁻⁵M。在高于其Ki值的浓度下，α,β-MTDP和α,β-MTTP不抑制标记胸苷掺入培养细胞的DNA，而5'-AdThd则会抑制。在相同条件下，这三种化合物均抑制胸苷酸（TMP）的掺入。胸苷和TMP掺入的抑制是特异性的，因为脱氧鸟苷的掺入几乎不受5'-AdThd的抑制。这些结果表明，胸苷和TMP掺入的特异性抑制主要是由于细胞对这些底物的通透性降低，而不是由于胸苷激酶活性的抑制。
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