Effects of pH on cytotoxicity of carboquone.

To assess the effects of pH on the cytotoxicity of carboquone (CQ), use was made of the mouse tail skin and HeLa cells in culture. CQ had the most potent cytotoxic effect at pH 6 rather than at pH7 or 8. Regarding the interaction between 14C-CQ and HeLa cells, both the intracellular accumulation of free 14C-CQ and the ratio of bound 14C-CQ to total 14C-CQ uptake were enhanced at pH6. Among the fractionated biomolecules of DNA, RNA and protein, DNA was the most active in binding CQ, under the same conditions of pH. The 14C-CQ binding to nucleic acids at pH 6 was more apparent than was the binding to protein. Thus, the enhancement of CQ cytotoxicity at low pHs is probably due to an increase in the intracellular accumulation of free CQ as well as to an enhanced reactivity of CQ with DNA, within the ranges of a lower pH.