Wu R T, Okabe T, Kim S H, Suzuki H, Tanaka N
J Antibiot (Tokyo). 1985 Nov;38(11):1588-95. doi: 10.7164/antibiotics.38.1588.
Cadeguomycin markedly stimulated the uptake of thymidine, deoxycytidine and uridine into the acid-insoluble fraction of K562 human leukemic cells, but did not significantly affect adenosine incorporation. The enhancement of pyrimidine nucleoside uptake was 6 approximately 17 fold over the control. Aspartate incorporation into nucleic acid was not significantly blocked by the antibiotic, suggesting that the stimulation of pyrimidine nucleoside incorporation is not due to the inhibition of de novo pyrimidine nucleotide synthesis. Net DNA and RNA syntheses, observed by [32P]phosphate uptake, were not significantly affected by cadeguomycin. The enzymatic activity of thymidine, deoxycytidine and uridine kinases was higher in cadeguomycin-treated cells than in untreated cells, suggesting that the enhancement of pyrimidine nucleoside uptake occurs in the phosphorylation process. The stimulatory activity of cadeguomycin of thymidine uptake was reversed by guanosine and deoxyguanosine, but not by adenosine and deoxyadenosine, suggesting that intracellular metabolism and/or action of cadeguomycin is related to that of guanosine and deoxyguanosine. The stimulation of pyrimidine nucleoside incorporation by cadeguomycin was also found with YAC-1 cells, but not with the other cell lines. The enhancement effect of the antibiotic seems to be not directly related to its cytotoxicity.
卡德古霉素显著刺激胸苷、脱氧胞苷和尿苷摄取进入K562人白血病细胞的酸不溶性部分，但对腺苷掺入没有显著影响。嘧啶核苷摄取的增强比对照高约6至17倍。抗生素对天冬氨酸掺入核酸没有显著阻断作用，这表明嘧啶核苷掺入的刺激不是由于从头嘧啶核苷酸合成的抑制。通过[32P]磷酸盐摄取观察到的净DNA和RNA合成不受卡德古霉素的显著影响。在经卡德古霉素处理的细胞中，胸苷、脱氧胞苷和尿苷激酶的酶活性高于未处理的细胞，这表明嘧啶核苷摄取的增强发生在磷酸化过程中。鸟苷和脱氧鸟苷可逆转卡德古霉素对胸苷摄取的刺激活性，但腺苷和脱氧腺苷则不能，这表明卡德古霉素的细胞内代谢和/或作用与鸟苷和脱氧鸟苷的相关。在YAC-1细胞中也发现了卡德古霉素对嘧啶核苷掺入的刺激作用，但在其他细胞系中未发现。抗生素的增强作用似乎与其细胞毒性没有直接关系。
