Summary: Using [14Cldimethyloxazolidinedione ([14Cl DMO) and quantitative autoradiography, we estimated tissue pH (pH,) and intracellular pH (pHi) in nine regions of the normal rat brain and in intracerebrally implanted RG-2 gliomas, Calculations of regional pH" based on equilibrium tissue and arterial plasma r14CjDMO concen tration, ranged from 6,83 to 6,94; pHi' calculated as suming an extracellular water volume of 0,15 ml/g for gray matter and 0,11 mllg for white matter, ranged from 6,61 to 6,78, No consistent difference was found in pH, or pHi between white and gray matter regions, TumorAccumulating evidence that changes in intracel lular pH (pHj) may accompany or modulate a va riety of biochemical and biophysical processes (Busa and Nuccitelli, 1984) has led to a renewed interest in the measurement of pHj. Using 14C-la beled dimethyloxazolidinedione (DMO) and quan titative autoradiography. we obtained preliminary measurements of regional brain and tumor pH in normal rats and in rats with leptomeningeal tumor. In both control and tumor-bearing animals. white matter was slightly but consistently more acidic than gray matter, whereas tumor was more alkaline than any brain region examined (J unck et al.. 1981). Similar preliminary results were obtained in rats with intracerebrally implanted RG-2 gliomas (Rot tenberg et aI., 1984). These findings are somewhat surprising, given the characteristically high rate of
369tissue water content was determined by drying to con stant weight, and extracellular space water volume (Ve) was estimated with r14Clsucrose in nephrectomized rats using quantitative autoradiography. Tumor pH, ranged from 7.08 to 7,18, For Ve = 0.17 (measured), pH; was 6.94-7 ,06; for Ve = 0,30 (assumed), the corresponding range for pHi was 6,63-6,90, Thus. the RG-2 glioma is not more "acidic" than adjacent brain tissue and its "al kaline" pH, probably reflects a large extracellular water content and plasma-like extracellular pH. Key Words: Brain tumor pH-Quantitative autoradiography, anaerobic glycolysis and lactic acid production in tumor tissue (Warburg, 1930).The present study was undertaken to (a) extend our previous measurements of regional brain/tumor pH to intracellular pH, (b) define the uncertainty in
MATERIALS AND METHODSRG-2 tumor cells were implanted intracerebrally into male CDF rats using a freehand injection technique (Gro othuis et aI., 1983h). The cells. obtained from a frozen stock. were thawed and grown in tissue culture before being pelleted and resuspended for injection in methyl cellulose solution; � 10 -4 cells were injected in a total volume of 2 , .. d. Representative tumored animals were autopsied at 2 .. to 3 .. day intervals following an intravenous injection of Evans blue dye to aid in the identification of