Crespi C L, Seixas G M, Turner T, Penman B W
Gentest Corporation, Woburn, Massachusetts 01801.
Environ Mol Mutagen. 1990;15(2):71-7. doi: 10.1002/em.2850150203.
Sodium fluoride was found to induce gene-locus mutations at the thymidine kinase (tk) and hypoxanthine guanine phosphoribosyl transferase (hgprt) loci in human lymphoblastoid cells. A single, 28 hr exposure to up to 600 micrograms/ml sodium fluoride induced a concentration-dependent increase in mutant fraction at both gene loci and reduced cell survival to 12% relative to negative control cultures. When cells were exposed to sodium fluoride concentrations that were only minimally toxic using a 20 day treatment protocol, no detectable induction of mutation was ob-served at the hgprt locus, and induction of mutation was observed at the tk locus only for treatment with 65 micrograms/ml sodium fluoride; exposure to 50 and 35 micrograms/ml sodium fluoride did not induce detectable mutation. The assay protocol used was of sufficient statistical sensitivity to detect the level of mutation predicted based on a linear extrapolation of data obtained from a 28 hour exposure. The implications of these observations with regard to the extrapolability of mutagenicity data to low concentrations are discussed.
研究发现，氟化钠可在人淋巴母细胞的胸苷激酶（tk）和次黄嘌呤鸟嘌呤磷酸核糖转移酶（hgprt）基因座诱发基因位点突变。单次暴露于高达600微克/毫升的氟化钠28小时，可导致两个基因座的突变率呈浓度依赖性增加，且相对于阴性对照培养物，细胞存活率降至12%。当使用20天的处理方案，让细胞暴露于仅具有最低毒性的氟化钠浓度时，在hgprt基因座未观察到可检测到的突变诱导，仅在使用65微克/毫升氟化钠处理时，在tk基因座观察到突变诱导；暴露于50和35微克/毫升氟化钠未诱导可检测到的突变。所使用的检测方案具有足够的统计灵敏度，能够检测基于28小时暴露所获数据的线性外推预测的突变水平。本文讨论了这些观察结果对于将致突变性数据外推至低浓度的意义。
