GENOTOXIC EFFECTS OF CHRONIC FLUORIDE EXPOSURE

长期接触氟化物的基因毒性效应

基本信息

批准号：
3425301
负责人：
ANN J DUNIPACE
金额：
$ 2.21万
依托单位：
INDIANA UNIV-PURDUE UNIV AT INDIANAPOLIS
依托单位国家：
美国
项目类别：
财政年份：
1988
资助国家：
美国
起止时间：
1988-08-01 至 1989-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3425301
关键词：
dental caries inhibitor drug administration rate /duration drug adverse effect fluorine laboratory mouse mutagen testing mutagens sperm motility

项目摘要

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.

将氟化物用作牙科中的cariotatic剂是很好的建立，结果，它在多个交付系统中的使用（牙齿，嘴，凝胶，小儿补充剂，牙齿材料）正在稳步增加，随着患病率的降低许多国家都在报告龋齿。但是，现在了解氟化物的不利影响是不完整的，而且，随着其使用的增加，越来越需要清楚的确定氟化物暴露的水平和条件（如果有）可能会导致有毒作用。越来越多的科学信息表明氟化物可能引起多种可能的遗传毒性作用禁忌在龋齿预防中广泛使用。最多以前的研究使用了非常高的非生理学氟化剂量，并得出基于结论单个测试程序。结果，目前有一个很棒的关于遗传毒性的混乱和矛盾的交易氟化物的作用和诱变潜力。因此，我们的实验室进行了初步研究其中互补的一系列诱变测试程序被用来研究急性氟化物的遗传毒性作用接触;我们现在建议扩展这些方法来研究慢性氟化物暴露。三个在体内诱变中建立测试将用于：1）观察慢性氟化物的影响对多色的染色体结构的处理红细胞（微核测试）； 2）研究氟化物对慢性暴露期间小鼠的生殖细胞形态（精子异常测试）； 3）确定慢性氟化物的影响关于染色单体跨界的特定像差（姐妹染色单体交换研究）。该提议的最终目标研究是为了建立有关遗传毒性的结论性证据慢性氟化物暴露的结果，以确定任何遗传毒性作用，并将其重要性对不断增加的预防性和治疗用途的影响牙科中的氟化物。