Tamm I
J Cell Physiol. 1983 Jul;116(1):26-34. doi: 10.1002/jcp.1041160106.
Dose-response curves for the inhibition of heterogeneous nuclear RNA (hnRNA) synthesis in HeLa cells by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB; 5-100 microM; 30 min) are biphasic and indicate the existence of two subpopulations of hnRNA molecules, one highly sensitive and the other completely resistant, as previously reported for molecules greater than 1,000 nucleotides long (Tamm et al., 1976; Sehgal et al., 1976a). In the short-term experiments, the drug-sensitive synthesis of hnRNA was inhibited 50% at a DRB concentration of approximately 7 microM, and 70% at 20 microM, whereas drug-resistant synthesis, which comprises approximately 20% of total, continued at DRB concentrations as high as 100 microM. After 24 hr of DRB treatment in medium containing 5% fetal calf serum, the increase in cell number in the exponentially growing population was inhibited by only 42% at 20 microM DRB, and the formation of colonies of greater than or equal to ten cells was not decreased. DRB at 40 microM concentration decreased population growth by 76% and colony formation by 63%. Treatment with 60 microM DRB was sufficient to prevent a net increase in cell number and to reduce colony formation by 78%. After termination of treatment, the time required for the surviving population to begin rapid proliferation was directly related to the concentration of DRB used to treat cells and to the duration of treatment. After 24-hr treatment with 40 microM DRB, cultures recovered within 1 day, whereas after 60 microM DRB, 3-4 days were required. After 40-hr treatment with 60 microM DRB, 5-6 days were required for recovery, and after 80 microM DRB, 9-11 days. During the "dormant" period the cell number ranged from 15 to 60% of the initial number and was fairly stable for given conditions. After the "dormant" period, recovery was rapid. The population growth rate in cultures undergoing treatment with DRB is directly related to serum concentration; however, the recovery rate during the post-treatment period is unaffected by serum concentration.
5,6-二氯-1-β-D-呋喃核糖基苯并咪唑（DRB；5-100微摩尔；30分钟）对HeLa细胞中异质核RNA（hnRNA）合成的抑制剂量反应曲线呈双相，表明存在两个hnRNA分子亚群，一个高度敏感，另一个完全耐药，这与之前报道的长度大于1000个核苷酸的分子情况相同（Tamm等人，1976年；Sehgal等人，1976a）。在短期实验中，在DRB浓度约为7微摩尔时，hnRNA的药物敏感合成被抑制50%，在20微摩尔时被抑制70%，而占总量约20%的耐药合成在DRB浓度高达100微摩尔时仍继续。在含5%胎牛血清的培养基中用DRB处理24小时后，在20微摩尔DRB时，指数生长群体中的细胞数量增加仅被抑制42%，且大于或等于10个细胞的集落形成未减少。40微摩尔浓度的DRB使群体生长减少76%，集落形成减少63%。用60微摩尔DRB处理足以阻止细胞数量的净增加，并使集落形成减少78%。处理终止后，存活群体开始快速增殖所需的时间与用于处理细胞的DRB浓度及处理持续时间直接相关。用40微摩尔DRB处理24小时后，培养物在1天内恢复，而用60微摩尔DRB处理后，需要3-4天。用60微摩尔DRB处理40小时后，恢复需要5-6天，用80微摩尔DRB处理后，需要9-11天。在“休眠”期，细胞数量为初始数量的15%至60%，在给定条件下相当稳定。“休眠”期后，恢复迅速。用DRB处理的培养物中的群体生长速率与血清浓度直接相关；然而，处理后时期的恢复速率不受血清浓度影响。
