Cook J A, Fox M H
Department of Radiology and Radiation Biology, Colorado State University, Fort Collins 80523.
Cancer Res. 1988 May 1;48(9):2417-20.
Culturing Chinese hamster ovary cells in low pH (6.6) medium for several months altered the reproductive survival of these cells to combined low pH treatments and 42.0 degrees C heating. We isolated new pH-resistant cells (identified as pHV-2) with enhanced ability to grow and divide under a low pH (6.6) environment. Their growth characteristics include (a) a plating efficiency of 70%, (b) a doubling time of 16 to 17 h, and (c) a steady state intracellular pH 0.12 pH units higher than for cells grown at a normal pH of 7.3. The pHV-2 cells had 100- to 200-fold increases in survival after 5 h of heating compared to cells incubated at low pH (6.6) for 4 h prior to and during the heat treatments. In addition, they developed a significant degree of thermotolerance. We measured a progressive decline in the intracellular pH as a function of time at 42.0 degrees C. However, the decrease in the intracellular pH did not seem to be correlated with the increased heat sensitivity. The ability to select for low pH variants may have important implications in the extrapolation of in vitro hyperthermic data to the in vivo situation.
在低pH（6.6）培养基中培养中国仓鼠卵巢细胞数月，改变了这些细胞在低pH处理和42.0摄氏度加热联合作用下的生殖存活率。我们分离出了新的耐pH细胞（命名为pHV-2），其在低pH（6.6）环境下生长和分裂的能力增强。它们的生长特性包括：（a）接种效率为70%，（b）倍增时间为16至17小时，以及（c）稳态细胞内pH比在正常pH 7.3下生长的细胞高0.12个pH单位。与在热处理前和热处理期间于低pH（6.6）下孵育4小时的细胞相比，pHV-2细胞在加热5小时后的存活率提高了100至200倍。此外，它们产生了显著程度的耐热性。我们测量了在42.0摄氏度下细胞内pH随时间的逐渐下降。然而，细胞内pH的降低似乎与热敏感性的增加无关。选择低pH变体的能力可能对将体外高温数据外推至体内情况具有重要意义。
