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Thermotolerance and intracellular pH in two Chinese hamster cell lines adapted to growth at low pH

✍ Scribed by Miriam L. Wahl; Ronald A. Coss; Suzanne B. Bobyock; Dennis B. Leeper; Charles S. Owen


Publisher
John Wiley and Sons
Year
1996
Tongue
English
Weight
466 KB
Volume
166
Category
Article
ISSN
0021-9541

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✦ Synopsis


As an in vitro model for the low extracellular pH (pH,) which has frequently been observed in tumors, cell lines have been grown in a low-pH medium in order to allow cell adaptation to that milieu. Two Chinese hamster cell lines [Chinese hamster ovary (CHO) and Chinese hamster ovarian carcinoma (OvCa)] were compared, both of which acquired thermotolerance during 42Β°C heating in pH, = 7.3 buffer, but not in pH, = 6.7 medium unless grown at that pH long enough to become adapted. CHO cells, even when acutely acidified, showed higher intracellular pH (pH,) values in a suspension assay than OvCa cells, which confirmed the danger of comparing absolute values of pH, between cell lines. Despite this fundamental difference, relative changes in pHi were similar in that both lines showed a higher pHi in adapted than in unadapted cells, over the range of pH, values tested. The upregulation of pHi was statistically significant, but the two lines differed in the time frame over which adaptation occurred. OvCa cells acquired an enhanced ability to develop tolerance to 42" heat at pH, = 6.7 in 4 days, but the CHO cells acquired this ability more progressively, achieving a maximum ability at approximately 100 days. In contrast, both lines were able to upregulate their pH, within 4 hours of being exposed to pH 6.7 medium. A further indication of different biochemical mechanisms at work was the opposite effects seen on pH, in the two cell lines upon the removal of extracellular COJHCO; . The differential between adapted and unadapted OvCa cells was enhanced by removal of bicarbonate, whereas CHO cells seemed less stable and the data with greater scatter failed to show any difference between adapted and unadapted cells. o 1996 WiIey-Liss, Inc.


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Intracellular pH (pHi) homeostasis is crucial to cell survival. Cells that are chronically exposed to a low pH environment must adapt their hydrogen ion extrusion mechanisms to maintain their pHi in the physiologic range. An important component of the adaptation to growth at low pH is the upregulati