Bruch Joachim, Rehn Steffanie, Rehn Bernd, Borm Paul J A, Fubini Bice
Institute of Hygiene and Occupational Medicine, Essen University Clinic, Germany.
Int J Hyg Environ Health. 2004 Jul;207(3):203-16. doi: 10.1078/1438-4639-00278.
The hypothesis of widely differing lung damage due to commonly used types of quartz was studied in 16 samples of respirable quartzes (> 99% silica) from sites of the European quartz industry, using an in vitro test, the vector model. Two samples with high and 2 with low biological activities were identified and subsequently examined for their in vivo lung toxicity (inflammation, fibrosis, genotoxicity) and surface characteristics. Alveolar macrophages (AM) are considered the target cells of primary dust effects. The vector model mimics some of the elemental dust cell effects such as cell toxicity, effects on the metabolism and stimulatory effects, e.g., TNF alpha and dust-induced ROS secretion.
Doses of 15, 30, 60 and 120 microg dust per 10(6) AM were used together with the control dusts (quartz DQ12 and corundum). Testing parameters were LDH, glucuronidase, PMA forced ROS release, TNF alpha and dust induced ROS secretion. The main criterion for the selection of low or high activity samples was the secretion of TNF alpha.
(i) Apart from quartz samples with an activity close to that of DQ12, one also finds examples with a very low activity. (ii) In comparison particular parameters are linked with a specific dose response relationship and different dose points for the leveling off of the effects. The levels of TNF alpha represent a conspicuously broad response pattern; some samples induce secretion at the lowest dose and others are not active even at the highest dose investigated at already apparent toxicity. (iii) Regarding various parameters the dust samples led to distinct dose response profiles considered as vectors. The current study indicates that within the particle type "quartz fine dust" varying harmful doses and different elements of damage must be present. (iv) The lung damage of the subchronic animal assay coincides with in vitro tests thus confirming the concept of the vector model.
Threshold effects in the range of 15 - > or = 120 microg can be demonstrated for the discriminant vector TNF alpha, i.e. over 4 steps of dose doubling. These studies show very toxic quartzes but also quartzes of low biological activity comparable to corundum.
利用体外试验——载体模型，对欧洲石英行业场所采集的16份可吸入性石英样本（二氧化硅含量>99%）进行研究，以验证常用类型石英导致肺部损伤差异巨大这一假说。确定了2份高生物活性样本和2份低生物活性样本，随后对其体内肺毒性（炎症、纤维化、遗传毒性）及表面特征进行检测。肺泡巨噬细胞（AM）被视为粉尘初始效应的靶细胞。载体模型模拟了一些元素性粉尘对细胞的效应，如细胞毒性、对代谢的影响以及刺激效应，例如肿瘤坏死因子α（TNFα）和粉尘诱导的活性氧（ROS）分泌。
每10⁶个AM使用15、30、60和120微克粉尘的剂量，同时设置对照粉尘（石英DQ12和刚玉）。检测参数包括乳酸脱氢酶（LDH）、葡萄糖醛酸酶、佛波酯（PMA）诱导的ROS释放、TNFα以及粉尘诱导的ROS分泌。选择低活性或高活性样本的主要标准是TNFα的分泌情况。
（i）除了活性与DQ12接近的石英样本外，还发现了活性极低的样本。（ii）相比之下，特定参数与特定的剂量反应关系以及效应趋于平稳的不同剂量点相关。TNFα水平呈现出明显宽泛的反应模式；一些样本在最低剂量时就诱导分泌，而另一些样本即使在已显现毒性的最高研究剂量下也无活性。（iii）就各种参数而言，粉尘样本呈现出被视为载体的不同剂量反应曲线。当前研究表明，在“石英细粉尘”颗粒类型中，必定存在不同的有害剂量和不同的损伤因素。（iv）亚慢性动物试验中的肺部损伤与体外试验结果相符，从而证实了载体模型的概念。
对于判别载体TNFα，可证明在15 - ≥120微克范围内存在阈值效应，即剂量翻倍超过4个步骤。这些研究显示出毒性极强的石英，但也有生物活性与刚玉相当的低活性石英。
