Arbeitsgruppe Zellkulturtechnik, Gesellschaft für Biotechnologische Forschung, Mascheroder Weg 1, D-3300 Braunschweig, Germany.
Biotechnol Bioeng. 1992 Oct 20;40(8):934-46. doi: 10.1002/bit.260400810.
Intracellular analysis has been shown to be useful as a tool for control production processes based on in vitro cultivated hybridoma and recombinant animal cells. Nucleotides were found to present the best target as they reflect the exact physiological state of a culture. Following the progress of batch, perfused, and chemostat cultures cell specific regularities were found in various biochemical correlations which allowed the generation of three characteristic parameters based on the interaction of particular nucleotides: the nucleotide triphosphate (NTP) ratio ([ATP + GTP]/[UTP + CTP]), the uridine (U) ratio (UTP/UDP-GNAc), and the combined ratio NTP/U ([UDP-GNAc (ATP + GTP)/ UTP (UTP + CTP)]). These allowed a direct description of the growth cycle by means of specific values or behavior for every phase of the culture. In particular, the critical phase of entrance into the phase of reduced growth was predicted up to 24 h earlier than was possible with the classical method of microscopic cell control. A specific function for the application of in vitro cultivated processes is proposed with an NTP-to-U plot which combines the results obtained by the cell analysis and which offers a tool for the control and regulation of cell growth-derived procedures.
细胞内分析已被证明是一种有用的工具，可用于控制基于体外培养的杂交瘤和重组动物细胞的生产过程。核苷酸被发现是最佳的目标，因为它们反映了培养物的精确生理状态。在分批培养、灌注培养和恒化培养的进展过程中，在各种生化相关性中发现了细胞特异性规律，这些规律允许基于特定核苷酸的相互作用生成三个特征参数：三磷酸核苷酸（NTP）比([ATP+GTP]/[UTP+CTP])、尿苷（U）比(UTP/UDP-GNAc)和组合比 NTP/U([UDP-GNAc(ATP+GTP)/UTP(UTP+CTP)])。这些参数允许通过特定的值或培养物每个阶段的行为直接描述生长周期。特别是，进入生长减缓阶段的关键阶段可以提前 24 小时预测，这比传统的显微镜细胞控制方法更为准确。提出了一种应用于体外培养过程的特定功能，即 NTP 到 U 的绘图，该图结合了细胞分析的结果，并为细胞生长衍生过程的控制和调节提供了一种工具。
