Chinese hamster cell lines resistant to the cytotoxic action of fluoride

The proliferation and efficiency of colony formation of a Chinese hamster ovary cell line, CHO, was found to be inhibited by concentrations of fluoride greater than or equal to 10(-3) M. From mutagenized populations of CHO cells, clones were isolated that were from 1.6 to 13 times more resistant than the wild-type to the cytotoxic action of fluoride. The resistant clones were found to be stable in the absence of selection. The fluoride sensitivity of wild-type and fluoride resistant clones was not altered by changes in the pyruvate concentration in the culture medium, indicating that the cytotoxic effect of fluoride is not due to the action of fluoride on the glycolytic pathway. On the other hand, both the incorporation of 3H-leucine into acid precipitable material and the distribution of polyribosomes were sensitive only to fluoride concentrations that were cytotoxic, suggesting that the molecular basis of fluoride induced cytotoxicity in both wild-type and fluoride resistant cells is the sensitivity of protein synthesis to fluoride. At concentrations of fluoride at which the wild-type cells are inhibited but fluoride resistant cells are not, the intracellular concentration of fluoride in the fluoride resistant cells was found to be 1/5 to 1/10 that of the wild-type, suggesting that fluoride exclusion is the basis for resistance in the resistant lines.