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Comparison between Tumor pH and Cell Sensitivity to Heat in RIF-1 Tumors¹

Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California 94305

We have performed a direct comparison between tumor pH and cell survival in heated RIF-1 tumors growing intradermally in thighs of C3H mice. The pH of individual tumors was measured by inserting a microelectrode into the tumor center. After pH measurements, the tumorbearing legs were heated in a water bath (44.6°C, 30 min). We then excised a small piece of tumor tissue (20–30 mg) from the area where the tip of the microelectrode had been placed and cell survival was determined by in vitro cloning. In some animals, 3 or 5 g/kg of glucose were injected i.p. 1.5 h before heating, to decrease the tumor pH. The average pH before heating was 6.83, 6.68, and 6.51, respectively, for tumors in untreated animals, those given 3 g/kg glucose, or those given 5 g/kg glucose. After heating, the average surviving fractions were 9.91 x 10^-2, 4.72 x 10^-2, and 5.43 x 10^-3, respectively. The cell yield did not differ significantly among the three treatments. As the tumor pH decreased, the surviving fraction also decreased for each treatment group. The correlation coefficient between tumor pH and log surviving fraction was highly significant for heat plus 5 g/kg glucose and all the treatment groups. The slope of the regression line obtained by a least squares method was steepest for all the treatment groups, followed by the heat plus 5 g/kg glucose and heat plus 3 g/kg glucose groups. The smallest slope of the regression line was noted for tumors treated by heat alone. The study shows that the tumor sensitivity to heat is enhanced when the tumor pH is lower and that adaptation of cells to low pH conditions may play a role in determining the relationship between pH and cell kill in RIF-1 tumors.

¹ This research was supported in part by National Cancer Institute Grant CA 04542 and CA 19386. The work reported in this paper was undertaken during the tenure of an American Cancer Society-Eleanor Roosevelt-International Cancer Fellowship awarded by the International Union Against Cancer to M. H.

² Present address: Department of Radiology, Faculty of Medicine, Kyoto University, Kyoto, Japan. To whom requests for reprints should be addressed.

Received 4/20/88. Revised 3/13/89. Accepted 4/10/89.

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