pH-induced modification of BCNU toxicity on glial cells

A dose-response relationship for the dependence of the cytotoxic activity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) on extracellular pH has been established. The hypothesis, that the integral dose of the rapidly degrading BCNU determines cytotoxicity, has been examined. Human glial cells exhibited lower survival rates for BCNU exposure at pH 6.5 and pH 6.7, compared to pH 7.4. This effect can be explained by the more rapid decay of BCNU at pH 7.4, leading to a lower integral dose. However, the determination of BCNU decay constants for different pH values and calculation of the integral exposure dose reveal that tolerance to BCNU is increased with decreasing pH.