Matsumoto M, Kawahara T, Tsuda M, Ohkubo T, Kamiguchi H, Yamamura M
Department of Biochemistry, Tokai University School of Medicine, Kanagawa, Japan.
Cancer Lett. 1992 Apr 30;63(3):221-8. doi: 10.1016/0304-3835(92)90264-v.
The cytotoxicity of 1-beta-D-arabinofuranosylcytosine (ara-C) in combination with hydroxyurea (HU) or 2'-deoxyguanosine (GdR) on human gastric carcinoma MK-1 cells and colon carcinoma HT-15 cells was studied. Synergistic interaction between ara-C and HU on MK-1 cells and HT-15 cells, or ara-C and GdR on MK-1 cells was shown using the combination index method. HU increased the accumulation of ara-C triphosphate (ara-CTP) in the acid-soluble pool and diminished the cellular deoxyCTP (dCTP) pool. HU had no effect on the incorporation of ara-C into DNA and RNA. These results indicate that HU-induced elevation in ara-CTP and decrease in dCTP are the basis for synergy among ara-C and HU in MK-1 cells. GdR diminished cellular dCTP slightly, but it decreased the accumulation of ara-CTP in the acid-soluble pool and did not increase the incorporation of ara-C into DNA. On the other hand, ara-C increased cellular deoxyGTP (dGTP) level in the presence of GdR. These results indicate that synergy between ara-C and GdR is mediated through increased cellular dGTP which might inhibit DNA synthesis directly.
研究了1-β-D-阿拉伯呋喃糖基胞嘧啶（阿糖胞苷，ara-C）与羟基脲（HU）或2'-脱氧鸟苷（GdR）联合对人胃癌MK-1细胞和结肠癌HT-15细胞的细胞毒性。采用联合指数法显示了阿糖胞苷与HU对MK-1细胞和HT-15细胞，或阿糖胞苷与GdR对MK-1细胞之间的协同相互作用。HU增加了酸溶性池中阿糖胞苷三磷酸（ara-CTP）的蓄积，并减少了细胞脱氧胞苷三磷酸（dCTP）池。HU对阿糖胞苷掺入DNA和RNA没有影响。这些结果表明，HU诱导的ara-CTP升高和dCTP降低是阿糖胞苷与HU在MK-1细胞中协同作用的基础。GdR轻微降低了细胞dCTP，但它减少了酸溶性池中ara-CTP的蓄积，并且没有增加阿糖胞苷掺入DNA。另一方面，在存在GdR的情况下，阿糖胞苷增加了细胞脱氧鸟苷三磷酸（dGTP）水平。这些结果表明，阿糖胞苷与GdR之间的协同作用是通过增加细胞dGTP介导的，这可能直接抑制DNA合成。
