Exposure to coarse, fine, and ultrafine particles is associated with adverse population health impacts. We investigated whether size-fractionated particles collected repeatedly in the vicinity of industrial (steel mills and associated coking operations, wastewater treatment), high traffic, and residential areas display systematic differences in biological potency. Particulate matter (PM<0.1, PM0.1–0.5, PM0.5–2.5, PM2.5–10, PM>10) samples collected at sites within Windsor, Ontario, were screened for biological potency in human A549 lung epithelial and murine J774A.1 macrophage-like cells using cytotoxicity bioassays (cellular ATP, resazurin reduction, lactate dehydrogenase (LDH) release), cytokine production, and transcript profiles. Potency was determined from the slope of each dose-effect relationship. Cytotoxic potency varied across size fractions and within a fraction across sites and sampling periods, suggesting that particle composition, in addition to size and mass, affected particle toxicity. While ATP and LDH profiles showed some similarity, resazurin reduction (a measure of metabolic activity) exhibited a unique pattern of response, indicating that the cytotoxicity assays were sensitive to distinct particle characteristics. Chemical speciation varied in relation to prevailing winds, consistent with enrichment of source emissions (e.g. higher metal and polycyclic aromatic hydrocarbon content downwind of the industrial site). Notwithstanding this variability, site-dependent differences in particle toxicity were evident, including greater potency of coarse fractions at the industrial site and of ultrafine particles at the traffic site (Site × Size interactions, p < 0.05). Regression of potency against particle constituents revealed correlations between resazurin reduction, induction of metal-responsive genes, and metal content, which were particularly strong for the coarse fraction, and between cytokine release and endotoxin, suggesting that these factors were important drivers of biological effects that explain, at least in part, the contrasting potencies of particles compared on an equivalent mass basis. The data show that 1) particle potency and composition can exhibit significant temporal variation in relation to source contributions; 2) sources may differentially impact the potency of specific size fractions; and 3) particle constituents, notably metals and endotoxin, may elicit distinct biological responses. Together, the data are consistent with the notion that sources and composition, in addition to size and mass concentration, are relevant to particle toxicity.

中文翻译：

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在一个小城市区域内反复收集的大小分级的颗粒物的细胞毒性和炎性潜力。

暴露于粗，细和超细颗粒会给人口健康带来不利影响。我们调查了在工业（钢厂和相关的焦化操作，废水处理），交通拥挤和居民区附近反复收集的大小分级的颗粒是否显示出系统的生物效价差异。筛选在安大略省温莎市内地点采集的颗粒物（PM <0.1，PM0.1-0.5，PM0.5-2.5，PM2.5-10，PM> 10）样品对人A549肺上皮和鼠的生物学效价使用细胞毒性生物测定法（细胞ATP，刃天青还原酶，乳酸脱氢酶（LDH）释放），细胞因子生成和转录物谱分析检测J774A.1巨噬细胞样细胞。从每种剂量效应关系的斜率确定效价。细胞毒性的效力随大小分数的变化以及在部位和采样周期的分数之内变化，这表明除了大小和质量之外，颗粒成分还会影响颗粒毒性。尽管ATP和LDH谱图显示出一些相似性，但刃天青的还原（一种代谢活性的量度）表现出独特的响应模式，表明细胞毒性测定法对不同的颗粒特征敏感。化学形态随盛行风而变化，这与排放源的丰富化相一致（例如，工业现场顺风方向的金属和多环芳烃含量较高）。尽管存在这种可变性，但颗粒毒性的位置依赖性差异还是很明显的，包括工业现场的粗级分和交通现场的超细颗粒的更大效能（站点×尺寸相互作用，p <0.05）。对颗粒成分的效力的回归显示刃天青减少，金属反应性基因的诱导和金属含量之间的相关性（对于粗粒级分而言尤为强烈）以及细胞因子释放和内毒素之间的相关性，表明这些因素是生物学效应的重要驱动力，至少部分地解释了以等效质量为基础进行比较的粒子的对比效力。数据表明：1）粒子的效能和组成可能会显示与源贡献有关的重大时间变化；2）来源可能会不同地影响特定大小部分的效力；和3）颗粒成分，特别是金属和内毒素，可能引起不同的生物学反应。总之，这些数据与这样的观念是一致的，即除了大小和质量浓度以外，来源和组成还与粒子毒性有关。