The effect of age on crystalline silica-induced pulmonary toxicity

The effect, if any, of age on the pulmonary toxicity induced by Min-U-Sil 5 crystalline silica exposure was investigated in rats. As part of the study, the changes in global gene expression profiles in the blood and lungs of the animals were determined. To conduct these studies, to determine if age influences the pulmonary response to crystalline silica exposure, two different age groups of healthy, male F344 rats were used. In this study the young age group of rats (6 months old at the time of exposure) was exposed to either air or crystalline silica (Min-U-Sil 5) (15 mg/m3, 6 hours/day, 5 days) by whole body inhalation. The young age group of rats simulates a group of workers who would be 18 to 20 years old. At two crystalline silica post-exposure time periods (1-day and 6-months) animals were euthanized and pulmonary inflammatory, cytotoxic, and oxidant responses were determined. Analysis of bronchoalveolar lavage parameters of toxicity such as oxidant generation and inflammation revealed significant changes in pulmonary toxicity in the crystalline silica exposed rats compared with the time-matched, air exposed control rats. The blood gene expression profiles showed only minimal changes, at both the time points, in the crystalline silica exposed rats compared with the controls. Specifically, there were a total of 5 genes significantly differentially expressed (fold change >1.5 and FDR p<0.05) in the one-day post-exposure group and no significantly differentially genes in the 6-month post-exposure group. However, the lung gene expression profiles showed substantial changes in the crystalline silica exposed animals at both one-day and 6-month post-exposure. Specifically, there were a total of 385 genes significantly differentially expressed (fold change >1.5 and FDR p<0.05) at the one-day post-exposure group and 317 genes significantly differentially expressed at the 6-month post-exposure. The data obtained from the present study demonstrated that crystalline silica inhalation exposure, under the conditions employed in the present study, resulted in significant changes in lung toxicity parameters and lung gene expression profile in the rats at both 1-day and 6-month post-exposure.本研究以大鼠为实验模型，探究年龄对Min-U-Sil 5型结晶二氧化硅（Min-U-Sil 5 crystalline silica）暴露诱导的肺毒性的影响。作为研究的核心内容之一，本研究测定了实验动物血液与肺部的全局基因表达谱变化。为明确年龄是否会影响机体对结晶二氧化硅暴露的肺脏应答反应，本研究选取两个不同年龄组的健康雄性F344大鼠（F344 rats）开展实验。其中年轻组大鼠在暴露时为6月龄，该组可模拟18至20岁的工人群体。年轻组大鼠通过全身吸入法暴露于空气或Min-U-Sil 5型结晶二氧化硅环境中，暴露参数为15 mg/m³、每日6小时、持续5天。分别在结晶二氧化硅暴露后1天与6个月两个时间点处死动物，测定其肺部炎症、细胞毒性与氧化应激应答水平。对支气管肺泡灌洗（bronchoalveolar lavage）的毒性相关参数（如氧化产物生成与炎症反应）进行分析后发现，与时间匹配的空气暴露对照组大鼠相比，结晶二氧化硅暴露大鼠的肺毒性存在显著差异。相较于对照组，结晶二氧化硅暴露大鼠在两个时间点的血液基因表达谱仅出现轻微变化。具体而言，暴露后1天组共有5个基因出现显著差异表达（倍数变化>1.5且错误发现率（FDR）校正p值<0.05），而暴露后6个月组未检测到显著差异表达基因。但肺部基因表达谱则显示，结晶二氧化硅暴露大鼠在暴露后1天与6个月两个时间点均出现显著变化：暴露后1天组共有385个基因出现显著差异表达，暴露后6个月组则有317个基因出现显著差异表达。本研究所得数据表明，在本研究采用的暴露条件下，结晶二氧化硅吸入暴露会使大鼠在暴露后1天与6个月时的肺毒性参数与肺部基因表达谱均出现显著改变。