Mehta K D, Gupta R S
Biochem Biophys Res Commun. 1985 Jul 31;130(2):910-7. doi: 10.1016/0006-291x(85)90503-0.
In Chinese hamster ovary cells, [3H]formycin B is metabolized into formycin B-5'-monophosphate, formycin A-5'-monophosphate and higher phosphorylated derivatives of formycin A which are incorporated into RNA. Mutants of CHO cells independently selected for resistance to various adenosine analogs viz. toyocamycin, tubercidin, 6-methylmercaptopurine riboside, which contain no detectable activity of adenosine kinase (AK) in cell extracts, all exhibited between 2- to 3-fold increased resistance to formycin B. Formycin B-resistant mutants of CHO cells are also affected in AK, as indicated by the absence of AK activity in cell extracts. Both types of AK- mutants showed reduced uptake and phosphorylation of [3H]formycin B in comparison to the parental (AK+) cells. In addition, toxicity of formycin B towards CHO cells was reduced in presence of adenosine in a concentration dependent manner. These observations strongly indicate that in CHO cells, formycin B is phosphorylated via AK and that like other nucleoside analogs its phosphorylation may be essential for the drugs cellular toxicity.
在中国仓鼠卵巢细胞中，[3H] 福米霉素 B 被代谢为福米霉素 B - 5'-单磷酸、福米霉素 A - 5'-单磷酸以及福米霉素 A 的更高磷酸化衍生物，这些衍生物会掺入 RNA 中。独立筛选出的对各种腺苷类似物（即丰加霉素、杀结核菌素、6 - 甲基巯基嘌呤核苷）具有抗性的中国仓鼠卵巢细胞突变体，其细胞提取物中未检测到腺苷激酶（AK）活性，所有这些突变体对福米霉素 B 的抗性均增加了 2 至 3 倍。中国仓鼠卵巢细胞的福米霉素 B 抗性突变体在 AK 方面也受到影响，这表现为细胞提取物中缺乏 AK 活性。与亲代（AK +）细胞相比，这两种类型的 AK 突变体对 [3H] 福米霉素 B 的摄取和磷酸化均减少。此外，在存在腺苷的情况下，福米霉素 B 对中国仓鼠卵巢细胞的毒性以浓度依赖的方式降低。这些观察结果有力地表明，在中国仓鼠卵巢细胞中，福米霉素 B 通过 AK 进行磷酸化，并且与其他核苷类似物一样，其磷酸化可能是该药物细胞毒性所必需的。
