Borodina V M, Kir'ianova E A, Zelenin A V, Reshetov P D, Chupova L A
Antibiotiki. 1981 Dec;26(12):915-9.
Significant changes in the nucleus structure, complete suppression of the mitotic activity, markedly decreased synthesis of RNA (by 70--80 per cent according to incorporation of 3H-uridine) and decreased levels of DNA (by 40 per cent according to olivomycin binding) were observed in the fibroblasts cultivated in vitro due to exposure to actinoxanthine in an amount of 50 microgram/ml. The data indicate direct damaging effect of the drug on the cell chromatin. The above nuclear changes were also observed after a short-term exposure of the cells to the drug (up to 5 minutes). Still, they became evident only after the subsequent incubation of the cells in a pure culture medium for at least 15 minutes. No such changes in the nucleus structure were detected when after the 5-minute exposure to actinoxanthine the cells were exposed to trypsin for 3 minutes. When the time of exposure to actinoxanthine was longer (15 minutes and higher), trypsin suppressed the manifestation of the above nuclear changes. The two-stage mechanism of the damaging effect of actinoxanthine on the chromatin of the cells cultivated in vitro is discussed. The damaging effect of actinoxanthine on the cells begins from binding of the drug with the cell membrane. After that a short incubation period follows and then the characteristic changes in the nucleus structure appear.
在体外培养的成纤维细胞中,当暴露于浓度为50微克/毫升的放线黄嘌呤时,观察到细胞核结构发生显著变化,有丝分裂活性完全受到抑制,RNA合成明显减少(根据3H-尿苷掺入量减少70%-80%),DNA水平降低(根据橄榄霉素结合量减少40%)。这些数据表明该药物对细胞染色质有直接损伤作用。在细胞短期暴露于该药物(长达5分钟)后,也观察到了上述细胞核变化。然而,这些变化仅在随后将细胞在纯培养基中孵育至少15分钟后才变得明显。当细胞在暴露于放线黄嘌呤5分钟后再暴露于胰蛋白酶3分钟时,未检测到细胞核结构有此类变化。当暴露于放线黄嘌呤的时间更长(15分钟及以上)时,胰蛋白酶会抑制上述细胞核变化的表现。文中讨论了放线黄嘌呤对体外培养细胞染色质损伤作用的两阶段机制。放线黄嘌呤对细胞的损伤作用始于药物与细胞膜的结合。之后是一段短暂的孵育期,然后细胞核结构出现特征性变化。