Abstract
We have observed that low pH can substantially potentiate the cytotoxic effect of the bioreductive drug SR4233 in aerobic HT-29 human tumour cells. No such potentiation was observed under hypoxic conditions. This pH effect might be relevant both to the therapeutic effectiveness and to the normal tissue toxicity of this new agent.
Highlights
The cells were incubated at 37°C for 1 h in complete medium containing 1000 LM or 40 tlM SR4233 for aerobic or hypoxic conditions, respectively
These conditions were chosen to yield approximately equivalent cell kill at pH 6.6 and they illustrate the striking potentiation of SR4233 cytotoxicity that occurs with hypoxic conditions
The cytotoxic effect of 1000 JSM SR4233 is strongly potentiated by low pH; the cell kill at pH 6.0 is approximately 300-fold greater than at pH 7.4
Summary
The cells were incubated at 37°C for 1 h in complete medium containing 1000 LM or 40 tlM SR4233 for aerobic or hypoxic conditions, respectively. These conditions were chosen to yield approximately equivalent cell kill at pH 6.6 and they illustrate the striking potentiation of SR4233 cytotoxicity that occurs with hypoxic conditions. The cytotoxic effect of 1000 JSM SR4233 is strongly potentiated by low pH; the cell kill at pH 6.0 is approximately 300-fold greater than at pH 7.4. Low pH seems to have, if anything, a slightly protective effect against SR4233 cytotoxicit
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