GENOTOXIC EFFECTS OF CHRONIC FLUORIDE EXPOSURE

氟化物作为防龋剂在牙科中的应用很好。 建立，并因此在多个交付系统中使用 (牙膏、口香糖、凝胶、儿科补充剂、牙科 材料)正在稳步增加，而患病率下降 据报道，许多国家都有龋齿。然而，现在 关于氟化物的有害影响的知识是不完整的， 而且，随着它的使用越来越多，人们越来越需要明确 确定氟化物暴露的水平和条件，如果有的话， 可能会造成毒害。 越来越多的科学信息表明，氟化物 会导致多种遗传毒性效应，这可能 禁忌它在防龋术中的广泛使用。多数 以前的研究使用了非常高的、非生理学的 氟化物的剂量，并得出结论，仅基于 一个单一的测试程序。因此，目前有一个很大的 关于基因毒素的混乱和矛盾的处理 氟化物的效应和诱变潜力。 正因为如此，我们实验室进行了初步研究。 其中一系列相辅相成的突变检测程序 用来研究急性氟化物的遗传毒性效应 暴露；我们现在建议将这些方法扩展到研究 慢性氟化物暴露。三种已确定的体内致突变性 试验将用于：1)观察慢性氟化物的影响 多染色质染色体结构的处理 红细胞微核试验；2)研究氟对小鼠的影响 慢性暴露小鼠的生殖细胞形态(精子 异常试验)；以及3)确定慢性氟的影响 关于染色单体交叉(姐妹)的特殊像差 染色单体交换研究)。这项提议的最终目标是 研究旨在建立关于遗传毒性的确凿证据 慢性氟暴露的结果，以确定其性质 任何遗传毒性影响，以及这些影响的重要性 对日益增加的预防和治疗用药的影响 牙科中的氟化物。

The use of fluoride as a cariostatic agent in dentistry is well established, and, as a result, its use in multiple delivery systems (dentifrices, mouthrinses, gels, pediatric supplements, dental materials) is steadily increasing with a decreasing prevalence of dental caries being reported in many countries. However, present knowledge of the detrimental effects of fluoride is incomplete, and, as its use increases, there is a growing need to clearly establish what levels and conditions of fluoride exposure, if any, may cause toxic effects. There is increasing scientific information suggesting that fluoride can cause a variety of genotoxic effects which may contraindicate its widespread use in caries prevention. Most previous investigations have used very high, non-physiological doses of fluoride and have based conclusions on the results of only a single test procedure. As a result, there is currently a great deal of confusion and contradiction regarding the genotoxic effects and mutagenic potential of fluoride. Because of this, our laboratory has conducted preliminary studies in which a complementary series of mutagenic test procedures were used to investigate the genotoxic effects of acute fluoride exposure; we propose now to extend these methodologies to study chronic fluoride exposure. Three established in vivo mutagenicity tests will be used to: 1) observe the influence of chronic fluoride treatment on the structure of chromosomes in polychromatic erythrocytes (Micronucleus Test); 2) study the fluoride effects on germ cell morphology of mice during chronic exposure (Sperm Abnormality Test); and 3) determine the effect of chronic fluoride on the specific aberration of chromatid crossover (Sister Chromatid Exchange studies). The ultimate goal of this proposed study is to establish conclusive evidence regarding genotoxic results of chronic fluoride exposure, to determine the nature of any genotoxic effects, and to relate the significance of these effects to the increasing prophylactic and therapeutic uses of fluoride in dentistry.