EFFECTS OF LEAD ON SALIVARY GLANDS AND DENTAL CARIES

铅对唾液腺和龋齿的影响

• 批准号: 6104907
• 负责人: WILLIAM H BOWEN
• 金额: $ 28.06万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-07-01 至 2001-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6104907
• 关键词: calcium flux; calcium metabolism; dental caries; embryo /fetus toxicology; growth /development; laboratory rat; lead poisoning; metal metabolism; pathologic process; salivary glands

High blood lead levels are among the most prevalent childhood conditions and the most prevalent environmental threat to the health of children in the United States" (HEALTHY PEOPLE 2000, p. 319). Toxicity from lead can be manifested in virtually every organ system. Lead and other heavy metals interfere with normal Ca2+ metabolism. Perturbation of Ca2+ metabolism has severe consequences on salivary gland function, amelogenesis. and dentinogenesis. Once lead enters the cell, its toxic effects are most likely mediated by activating protein kinase C and/or Ca2+ calmodulin- dependent protein kinase by modifying reactive sulfhydryl groups or by binding to Ca2+ binding sites on ion transporters. Salivary gland hypofunction is clearly related to increased caries. Lead may affect cariogenesis directly by competing for calcium binding sites, thereby affecting demineralization and remineralization of enamel. Lead in saliva and plaque may result in the formation of lead fluoride which is essentially insoluble, rendering fluoride unavailable for its caries protective effect. We propose determining the influence of prenatal exposure to lead on susceptibility to dental caries and also explore the effect of lead on salivary gland development and function as determined by induced flow rate and selected organic and inorganic constituents. Calcium metabolism subsequent to lead and heavy metal exposure will be monitored by observing steps involved in stimulation-induced [Ca2+) mobilization in salivary acinar cells by measuring: l) inositol phosphate formation, 2) intracellular Ca2+ release, and 3) divalent cation influx. Possible influence of lead and heavy metals on Ca2+-regulated ion transport mechanisms associated with fluid secretion will be determined by assaying intracellular pH [Cl-] and [Na+]. Knowledge gained from these studies could have a major societal impact, enhance our understanding of the etiology and pathogenesis of dental caries, and the effects of lead and heavy metals on salivary gland physiology.

高血铅水平是最普遍的儿童疾病之一 以及对儿童健康最普遍的环境威胁， （《健康人》，2000年，第319页）。铅的毒性可以 在几乎所有的器官系统中都有表现。铅和其他重金属 干扰正常钙代谢。Ca 2+代谢的紊乱 严重影响唾液腺功能和牙釉质形成。和 牙本质形成一旦铅进入细胞，其毒性作用是最 可能通过激活蛋白激酶C和/或Ca 2+钙调蛋白介导。 通过修饰反应性巯基或通过 与离子转运蛋白上的Ca 2+结合位点结合。唾液腺 功能减退明显与龋齿增加有关。铅可能影响 直接通过竞争钙结合位点， 影响釉质的脱矿和再矿化。唾液中的铅 牙菌斑可能导致氟化铅的形成， 基本上不溶，使氟化物不能用于其龋齿 保护作用。我们建议确定产前的影响 铅暴露对龋齿易感性的影响，并探讨 铅对唾液腺发育和功能影响 诱导流速和选定的有机和无机成分。钙 将监测铅和重金属暴露后的代谢情况 通过观察刺激诱导的[Ca 2 +]动员的步骤， 通过测量唾液腺泡细胞：1）磷酸肌醇形成，2） 胞内Ca 2+释放和3）二价阳离子流入。可能 铅和重金属对钙离子转运影响 与液体分泌相关的机制将通过测定 细胞内pH [Cl-]和[Na+]。从这些研究中获得的知识 可能会产生重大的社会影响，增强我们对 龋病的病因和发病机制，以及铅和 重金属对唾液腺生理的影响