EFFECTS OF LOW-DOSE CADMIUM ON PROSTATE CELLS

低剂量镉对前列腺细胞的影响

• 批准号: 6164041
• 负责人: WAYNE B JONAS
• 金额: $ 36.74万
• 依托单位: HENRY M. JACKSON FDN FOR THE ADV MIL/MED
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-01 至 2003-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6164041
• 关键词: alternative medicine; antineoplastics; cadmium; cytoprotection; environmental exposure; environmental toxicology; gene expression; heat shock proteins; metallothionein; neoplastic transformation; prostate; prostate neoplasms; tissue /cell culture

DESCRIPTION (Adapted from Applicant's Abstract): Chronic low-level exposure to environmental toxins, including cadmium, is an enormous and growing problem in the industrialized world. cadmium is a potent carcinogen in rodents and has also been linked to human lung and prostate cancer, a malignant disease with an increasing mortality. In vitro models of experimental cadmium toxicity is proposed to study the molecular mechanisms of prostate epithelia cell injury and repair. One promising strategy for protection from toxins is the use of low doses of chemicals to enhance cell tolerance and recovery, a phenomenon known as hormesis. This strategy is also the theoretical basis for the observed effects in homeopathy. The homeopathic literature has for decades reported the use of cadmium for the treatment of cancer. Low and very-low-dose cadmium doses induce gene expression of protective proteins (metallothonein (MT) and heat shock) and reduce mortality to toxic doses both in vitro and in vivo. In preliminary research it was demonstrated that medium dose cadmium exposure altered gene expression patterns, enhanced protective protein (MT) levels and protected against acute cadmium toxicity in human prostate epithelial cells. The objective of this project is to determine the tissue specific molecular signatures produced by low dose levels of cadmium and to identify the optimal doses that protect against toxic injury. When completed we will have developed a novel and highly sensitive approach for detecting and treating toxic exposures. We will also have developed, for the first time, a systematic model for the scientific study of protective hormesis and homeopathy in environmental toxicology and prostate disease.

描述（改编自申请人摘要）：慢性低水平暴露于 环境毒素，包括镉，是一个巨大的和日益严重的问题， 工业化世界。镉是啮齿动物体内的一种强致癌物质， 还与人类肺癌和前列腺癌有关，这是一种恶性疾病， 增加死亡率。实验性镉毒性的体外模型是 研究前列腺上皮细胞损伤的分子机制 和修复。一个有希望的策略，保护免受毒素是使用低 剂量的化学物质，以提高细胞的耐受性和恢复，一种现象， 作为毒物兴奋效应。这一战略也是观察到的理论基础 顺势疗法的效果顺势疗法文献几十年来一直报道， 镉在癌症治疗中的应用。低剂量和极低剂量镉剂量 诱导保护性蛋白（金属硫蛋白（MT）和热）基因表达 休克）和降低体外和体内毒性剂量死亡率。在 初步研究表明，中等剂量镉暴露 改变基因表达模式，增强保护蛋白（MT）水平， 在人前列腺上皮细胞中保护免受急性镉毒性。 本项目的目的是确定组织特异性分子 低剂量镉产生的信号，并确定最佳的 保护免受毒性伤害的剂量。完成后，我们将开发 一种新的高灵敏度的检测和治疗有毒物质的方法， 暴露。我们还将首次开发出一个系统的模型， 环境中保护性兴奋效应和顺势疗法的科学研究 毒理学和前列腺疾病。