Regulation of intracellular pH in tumor cell lines: influence of microenvironmental conditions
Boyer, M.J.; Tannock, I.F.
Cancer Research 52(16): 4441-4447
1992
ISSN/ISBN: 0008-5472 PMID: 1322790 Document Number: 392855
The effect of microenvironmental factors on the regulation of intracellular pH (pHi) in MGH U1 cells and EMT-6 cells was studied using the fluorescent pH probe 2',7'-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein. Na+/H+ exchange and Na+-dependent Cl-/HCO3- exchange were found to be present in both cell types. The activity of bot6h exchangers was dependent on pHi, with low levels of activity at neutral pH and an increase in activity as pHi fell. The level of extracellular pH (pHe) also influenced the operation of the exchangers, with a fall in activity as pHe was reduced over the range 7.4-6.6. This effect was more marked for the Na+-dependent Cl-/HCO3- exchanger than for the Na+/H+ antiporter, suggesting that under conditions of reduced pHe the Na+/H+ antiporter is the major mechanism for regulaton of pHi. Neither 6 h of radiobiological hypoxia nor variations in the extracellular [Ca2+] over the range 1-6 mM had an affect on the regulation of pHi, while extracellular lactate (5-10 mM) caused a small, concentration-dependent decrease in the combined activity of both exchangers. We conclude that under the microenvironmental conditions found in some regions of tumors, Na+/H+ exchange may be the major method of regulation of pHi.