Mechanisms of Pleural and Pulmonary Toxicity of Indium Compounds

铟化合物的胸膜和肺部毒性机制

• 批准号: 9143475
• 负责人: DANIEL MORGAN
• 金额: $ 26.25万
• 依托单位: NATIONAL INSTITUTE OF ENVIRONMENTAL HEALTH SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9143475
• 关键词: Agar; Alveolar; Ames Assay; Asbestos; Biological Assay; Breathing; Carcinoma; Cell Proliferation; Cells; Characteristics; Chronic; Data; Epithelial; Exposure to; Fiber; Gene Expression; Goals; Growth; Human; Hyperplasia; In Vitro; Indium; Industry; Inhalation Exposure; Ions; Link; Lung; Lung Neoplasms; Malignant - descriptor; Malignant Neoplasms; Matrix Metalloproteinases; Mesothelial Hyperplasia; Mesothelium; Metals; Micronucleus Tests; Mus; Particulate; Pleural; Rattus; Reverse Transcriptase Polymerase Chain Reaction; Running; Serum; Severities; Toxic effect; adenoma; base; cancer cell; carcinogenicity; exposed human population; genotoxicity; in vitro Model; indium phosphide; indium tin oxide; insight; macrophage; man; matrigel; particle

Studies involving indium-containing particles (ICPs) indium phosphide (InP) and indium tin-oxide (ITO) were completed. Studies are in progress to determine if prolonged chronic exposure to sub-lethal concentrations (0.5 and/or 1 M) of soluble InCl3 can transform human lung epithelial (HPL-1D) cells into malignant cancer cells in vitro. The purpose of this carcinogenicity study is based on previous chronic inhalation data in rats and mice showing that InP and ITO particles were highly carcinogenic to the lung combined with the fact that there is currently no cancer data linked to indium exposure in humans. As of week 38, increased expression of matrix metalloproteinases (MMPs) by indium-treated lung cells and morphologic changes suggest that transformation is occurring. Additional assays to examine the acquisition of cancer cell characteristics will include cell proliferation, serum-independent growth, colony formation in soft agar, invasion (using matrigel) and gene expression (using RT-PCR). The NTP is also running a micronucleus assay and Ames test to assess the genotoxicity of InCl3.

涉及含酰胺颗粒（ICP）磷酸二磷脂（INP）和依赖二氧化物（ITO）的研究完成了。正在进行研究，以确定长期慢性暴露于可溶性含有下致命浓度（0.5和/或1 m）的可溶性含量3可以将人类肺上皮（HPL-1D）细胞转化为恶性癌细胞的体外。这项致癌性研究的目的是基于大鼠和小鼠中先前的慢性吸入数据，表明INP和ITO颗粒具有高度致癌性，与目前尚无癌症数据有关的癌症数据与人类的依赖性相关。截至第38周，通过鉴别处理的肺细胞和形态学变化增加了基质金属蛋白酶（MMP）的表达，这表明正在发生转化。检查癌细胞特征的获取的其他测定将包括细胞增殖，血清独立的生长，软琼脂中的菌落形成，侵袭（使用Matrigel）和基因表达（使用RT-PCR）。 NTP还运行了微核测定法和AMES测试，以评估含有3的遗传毒性。

项目成果

Pleural effects of indium phosphide in B6C3F1 mice: nonfibrous particulate induced pleural fibrosis.

• DOI: 10.3109/01902140902980961
• 发表时间: 2009-12
• 期刊: Experimental lung research
• 影响因子: 1.7
• 作者: Kirby PJ;Shines CJ;Taylor GJ;Bousquet RW;Price HC;Everitt JI;Morgan DL
• 通讯作者: Morgan DL