HEALTH RISK ASSESSMENT OF ENVIRONMENTAL NANO PARTICLES USING MOLECULAR BIOLOGICAL METHODS

我们评估了分子生物学方法在环境纳米颗粒健康风险评估中的有效性。(1)选取暴露于柴油颗粒7个月或高浓度空气颗粒（CAPs） 3天的老龄大鼠（22 ~ 24月龄）的肺和心脏组织。DNA谱分析结果显示，暴露于柴油机排放的肺补体、巨噬细胞活化细胞因子、趋化因子、cinc2、血氧化酶和血管紧张素II受体、暴露于CAPs的肺补体、炎症相关成分和凝血相关项目、暴露于CAPs的心脏补体中DNA基因表达增加。DNA表达水平的增加并不一定与mRNA表达或蛋白质浓度相对应。暴露于柴油颗粒或cap的老年大鼠的生理和病理结果以及DNA和mRNA表达的变化仅显示出轻微的相关性。另一方面，用有机溶剂洗涤柴油颗粒（E-DEP）处理的大鼠肺部炎症相关细胞因子mRNA的表达高于未洗涤柴油颗粒（DEP）处理的大鼠。E-DEP的每重量颗粒面积比DEP大。这些发现支持了纳米颗粒比细颗粒对肺的毒性更大的假设。我们的研究结果表明，DNA谱分析有助于在纳米颗粒健康风险评估的第一步选择与疾病相关的生物标志物。随后，确定所选生物标志物的mRNA表达水平和蛋白质浓度。纳米颗粒毒性的最终健康风险评估应基于对分子生物学、生物化学、血液学、病理学和生理学数据的综合评估。

We evaluated the usefulness of molecular biological methods in the health risk assessment of environmental nanoparticles. (1) Lung and heart tissues were collected from aged rats (aged 22-24 months) that had been exposed to diesel particles for 7 months or concentrated air particles (CAPs) for 3 days. The results of DNA profile analysis showed increases in DNA gene expression in complements, macrophage activated cytokine, chemokine, CINC-2, hemoxidase, and angiotensin II receptor in the lung exposed to diesel emission, in complements, inflammation-related components and blood coagulation-related items in the lung exposed to CAPs, and in complements in the heart exposed to CAPs. The increases in DNA expression level did not necessarily correspond with mRNA expression or protein concentration. Physiological and pathological findings and changes in DNA and mRNA expression showed only slight correlations in aged rats exposed to diesel particles or CAPs. On the other hand, the expression of inflammation-related cytokine mRNA was higher in the lungs of rats treated with diesel particles washed with organic solvent (E-DEP) than in those of rats treated with unwashed particles (DEP). E-DEP had a larger particle area per weight than DEP. These findings support the hypothesis that nanoparticles have greater toxicity in the lung than fine particles. The results of our study suggested that DNA profile analysis are useful for the selection of disease-related biomarkers in the first step of the health risk assessment of nanoparticles. Following this, the levels of mRNA expression and protein concentration are confirmed for the selected biomarkers. The final health risk assessment of nanoparticle toxicity should be based on an overall evaluation of molecular biological, biochemical, hematological, pathological and physiological data.