Mankovitz R, Kisilevsky R, Florian M
Can J Genet Cytol. 1978 Mar;20(1):71-84. doi: 10.1139/g78-009.
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.
发现当氟化物浓度大于或等于10⁻³ M时，中国仓鼠卵巢细胞系（CHO）的增殖和集落形成效率受到抑制。从经诱变的CHO细胞群体中分离出的克隆，对氟化物细胞毒性作用的抗性比野生型高1.6至13倍。发现抗性克隆在无选择条件下是稳定的。培养基中丙酮酸浓度的变化未改变野生型和氟化物抗性克隆对氟化物的敏感性，这表明氟化物的细胞毒性作用不是由于氟化物对糖酵解途径的作用。另一方面，³H-亮氨酸掺入酸沉淀物质以及多核糖体的分布仅对具有细胞毒性的氟化物浓度敏感，这表明在野生型和氟化物抗性细胞中，氟化物诱导细胞毒性的分子基础是蛋白质合成对氟化物的敏感性。在野生型细胞受到抑制而氟化物抗性细胞未受抑制的氟化物浓度下，发现氟化物抗性细胞中的细胞内氟化物浓度是野生型的1/5至1/10，这表明氟化物外排是抗性细胞系中抗性的基础。
