Seagrave JeanClare, McDonald Jacob D, Reed Matthew D, Seilkop Steven K, Mauderly Joe L
Lovelace Respiratory Research Institute, Albuquerque, New Mexico 87108, USA.
Inhal Toxicol. 2005 Nov;17(12):657-70. doi: 10.1080/08958370500189529.
Air pollution exposure is associated with adverse health effects, but the causal components and mechanisms are unclear. We compared effects of daily exposure for 6 mo to diesel exhaust (DE) or hardwood smoke (HWS) at 4 concentrations between 30 and 1000 microg/(3) of total particulate matter, or filtered air, in male and female rats. Lung lavage fluid was assayed for toxicity indicators, cytokines, and glutathione. Statistical analyses included pairwise comparisons with control and exposure-related trends, modeled using techniques that facilitated evaluation of nonlinear exposure effects. Lactate dehydrogenase increased with exposure concentration in DE-exposed females, but in other groups, low exposure concentrations caused increases while higher concentrations had less effect. Total protein in the HWS-exposed males and females followed similar patterns. Alkaline phosphatase increased in DE-exposed females, but decreased in HWS-exposed males and females. Beta-Glucuronidase decreased in HWS- and DE-exposed males, but HWS-exposed females showed decreases at low exposure concentrations and weak increases at higher exposure concentrations. Macrophage inflammatory protein-2 decreased in HWS-exposed males and females and DE-exposed females. Tumor necrosis factor-alpha levels decreased in DE-exposed females and males, but HWS-exposed males showed small increases. DE did not affect total glutathione in either gender, but HWS decreased glutathione in females, while in males, increases at low exposure concentrations but not at higher exposure levels were observed. Thus, these two combustion emissions differentially affect lung responses, with gender affecting response patterns. Furthermore, effects may be nonmonotonic functions of exposure levels, with maximal responses in environmentally or occupationally relevant exposure ranges.
暴露于空气污染中会对健康产生不良影响，但其致病成分和机制尚不清楚。我们比较了雄性和雌性大鼠连续6个月每天暴露于4种浓度（总颗粒物浓度在30至1000微克/立方米之间）的柴油废气（DE）或硬木烟雾（HWS）或过滤空气中的影响。对肺灌洗液进行毒性指标、细胞因子和谷胱甘肽检测。统计分析包括与对照组的成对比较以及与暴露相关的趋势分析，采用有助于评估非线性暴露效应的技术进行建模。在暴露于DE的雌性大鼠中，乳酸脱氢酶随暴露浓度增加而升高，但在其他组中，低暴露浓度会导致升高，而高浓度的影响较小。暴露于HWS的雄性和雌性大鼠的总蛋白呈现相似模式。暴露于DE的雌性大鼠碱性磷酸酶升高，而暴露于HWS的雄性和雌性大鼠碱性磷酸酶降低。暴露于HWS和DE的雄性大鼠β-葡萄糖醛酸酶降低，但暴露于HWS的雌性大鼠在低暴露浓度时降低，在高暴露浓度时微弱升高。暴露于HWS的雄性和雌性大鼠以及暴露于DE的雌性大鼠中巨噬细胞炎性蛋白-2降低。暴露于DE的雌性和雄性大鼠肿瘤坏死因子-α水平降低，但暴露于HWS的雄性大鼠有小幅升高。DE对两性的总谷胱甘肽均无影响，但HWS降低了雌性大鼠的谷胱甘肽，而在雄性大鼠中，低暴露浓度时谷胱甘肽增加，高暴露水平时则未增加。因此，这两种燃烧排放物对肺部反应的影响不同，性别也会影响反应模式。此外，影响可能是暴露水平的非单调函数，在环境或职业相关的暴露范围内反应最大。
