PHENOTYPIC CONVERSION OF CULTURED MOUSE EMBRYO CELLS BY AZA PYRIMIDINE NUCLEOSIDES
PHENOTYPIC CONVERSION OF CULTURED MOUSE EMBRYO CELLS BY AZA PYRIMIDINE NUCLEOSIDES
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DOI：
10.1016/0012-1606(78)90273-7
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发表时间：
1978-01-01
影响因子：
2.7
通讯作者：
JONES, PA
中科院分区：
文献类型：
--
作者：
CONSTANTINIDES, PG;TAYLOR, SM;JONES, PA
C3 H/10 T1/2CL 8 [小鼠胚胎成纤维细胞]系的细胞本质上是非成肌细胞，当用低浓度的5-氮杂胞苷[一种用于癌症治疗的药物]处理时，它们形成功能性肌管。它们由单核前体融合而产生，而不是核内复制的结果。它们积累组织化学可检测的肌球蛋白ATP酶活性和能够结合放射性标记的α-乙酰胆碱受体。银环蛇毒素脱氧类似物5-氮杂-2“-脱氧胞苷在5-氮杂胞苷最大有效浓度的1/10诱导肌原性转化。这两种类似物诱导肌管形成和引起细胞毒性的能力受到某些嘧啶核苷共同治疗的强烈影响。这些效应与两种氮杂化合物代谢为磷酸化衍生物的要求以及基于其掺入DNA的作用机制一致。引起肌原性转化的类似物的浓度基本上不改变DNA、RNA或蛋白质合成的速率，如通过前体掺入完整细胞所测量的。在通过2种不同方法同步化的细胞中通过5-氮杂胞苷诱导肌管需要在S期早期的关键阶段用类似物进行处理。药物的作用机制似乎与特定的DNA合成有关。
Cells of the C3H/10T1/2CL8 [mouse embryo fibroblast] line, which are nonmyoblastic in nature, form functional myotubes when treated with low concentrations of 5-azacytidine [a drug used in cancer therapy]. They arise from the fusion of mononucleated precursors and not as a result of endoreplication. They accumulate histochemically detectable myosin ATPase activity and acetylcholine receptors capable of binding radioactively labeled .alpha.-bungarotoxin. The deoxy analog, 5-aza-2''-deoxycytidine, induced myogenic conversion at 1/10 of the maximally effective concentration of 5-azacytidine. The ability of both analogs to induce myotube formation and to cause cytotoxicity was strongly influenced by cotreatment with certain pyrimidine nucleosides. These effects were consistent with a requirement for metabolism of both aza compounds to phosphorylated derivatives and with a mechanism of action based on their incorporation into DNA. Concentrations of the analogs causing myogenic conversion did not substantially alter rates of DNA, RNA or protein synthesis as measured by precursor incorporation into intact cells. The induction of myotubes by 5-azacytidine in cells synchronized by 2 different methods required that treatment with the analog was carried out at a critical phase early in S phase. The mechanism of drug action appears to be linked to specific DNA synthesis.