GENOTOXIC EFFECTS OF CHRONIC FLUORIDE EXPOSURE

长期接触氟化物的基因毒性效应

• 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
• 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

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.

在牙科中使用氟化物作为防龋剂是很好的 因此，它在多种输送系统中的使用 （牙膏、漱口水、凝胶、儿科补充剂、牙科保健品） 材料）稳步增加， 龋齿在许多国家都有报道。 然而，目前 对氟化物的有害作用的了解是不完全的， 而且，随着其使用的增加，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， 可能会引起毒性作用。 越来越多的科学信息表明， 可引起多种遗传毒性效应， 禁忌其在龋齿预防中的广泛使用。 最 以前的研究使用了非常高的，非生理性的 剂量的氟化物，并已根据结果的结论，只有 单一测试程序。 因此，目前有一个很大的 关于遗传毒性的混乱和矛盾 氟化物的影响和致突变潜力。 正因为如此，我们的实验室已经进行了初步研究， 其中一系列补充的诱变试验程序 研究了急性氟中毒的遗传毒性效应 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）观察慢性氟的影响 多色染色体结构的处理 红细胞（微核试验）; 2）研究氟对 慢性暴露期间小鼠生殖细胞形态（精子 异常试验）; 3）确定慢性氟的影响 染色单体交换（Sister 染色单体交换研究）。 这一提议的最终目标是 研究旨在确立关于遗传毒性的结论性证据 结果慢性氟暴露，以确定性质 任何遗传毒性效应，并将这些效应的意义 对日益增加的预防和治疗用途的影响 牙科中的氟化物

项目成果

Genotoxic evaluation of chronic fluoride exposure: micronucleus and sperm morphology studies.

慢性氟化物暴露的基因毒性评估：微核和精子形态研究。

• DOI: 10.1177/00220345890680111101
• 发表时间: 1989
• 期刊: Journal of dental research
• 影响因子: 7.6
• 作者: Dunipace,AJ;Zhang,W;Noblitt,TW;Li,Y;Stookey,GK
• 通讯作者: Stookey,GK

Genotoxic evaluation of chronic fluoride exposure: sister-chromatid exchange study.

慢性氟化物暴露的基因毒性评估：姐妹染色单体交换研究。

• DOI: 10.1016/0165-7992(89)90040-7
• 发表时间: 1989
• 期刊: Mutation research
• 作者: Li,YM;Zhang,W;Noblitt,TW;Dunipace,AJ;Stookey,GK
• 通讯作者: Stookey,GK