Because acidic regions may coexist with hypoxic regions in solid tumors, we have studied the effect of acidic extracellular pH on the abilities of misonidazole, etanidazole, and cis-diamminedichloroplatinum(II) (CDDP) to radiosensitize hypoxic FSaIIC cells in vitro. For 1-h exposures to misonidazole prior to and during irradiation, the sensitizer enhancement ratios (SERs) were 2.10 ± 0.18 at 1 mM drug and 2.50 ± 0.16 at 5 mM drug at pH 7.40 but only 1.90 ± 0.14 and 2.30 ± 0.14, respectively, at pH 6.45. For entanidazole the SERs at pH 7.40 at 1 and 5 mM drug were 1.90 ± 0.13 and 2.40 ± 0.18, respectively, but only 1.25 ± 0.13 and 1.70 ± 0.17, respectively, at pH 6.45. The decrease in the SERs for both 2-nitroimidazole compounds was statistically significant (P < 0.01). When CDDP at concentrations of 1 and 5 μM was tested, SERs of 1.30 ± 0.15 and 1.60 ± 0.18, respectively, were observed at pH 7.40, and the increase was not significant at pH 6.45 (1.35 ± 0.15 and 1.80 ± 0.19, respectively). The cellular levels of misonidazole, etanidazole, and CDDP did not vary significantly at the environmental conditions tested. These results demonstrate that pH is a potentially important variable in the action of hypoxic cell radiosensitizing drugs and suggest that future evaluations of such agents should test the effects of pH.
Effect of Acidic pH on Radiosensitization of FSallC Cells in Vitro by Misonidazole, Etanidazole, or cis-Diamminedichloroplatinum (II)
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Terence S. Herman, Beverly A. Teicher, M. Raphael Pfeffer, Vrinda Khandekar, Rebekah M. Chapnick, Glenn S. Kalick, Amy Rabow; Effect of Acidic pH on Radiosensitization of FSallC Cells in Vitro by Misonidazole, Etanidazole, or cis-Diamminedichloroplatinum (II). Radiat Res 1 October 1990; 124 (1): 28–33. doi: https://doi.org/10.2307/3577690
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