Ishihara Y, Kyono H, Kohyama N, Otaki N, Serita F, Toya T, Kagawa J
Department of Hygiene and Public Health (I), School of Medicine, Tokyo Women s Medical University, Tokyo 162-8666, Japan.
Inhal Toxicol. 1999 Feb;11(2):131-49. doi: 10.1080/089583799197212.
The dimensions of man-made mineral fiber whiskers are similar to those of some kinds of asbestos. Thus these mineral fibers raise the concern for potential health hazard for workers exposed in the occupational environments. This study was designed to define acute biological effects of intratracheally administered titanium dioxide whiskers (TO1) compared with nonfibrous titanium dioxide (TOP) and UICC amosite (Ams), and their relations to acute lung inflammation in rats. The observed geometric mean length (microm) and width (microm) and geometric standard deviation are: TO1(2.1[2.0], 0.14[1. 53]); Ams (4.3[3.3], 0.31[1.9]); and TOP (50 nm, 1-2 microm aggregates). Ten-week-old Wistar-Jcl male rats received a single tracheal injection of test materials at doses between 0.05 and 1.0 mg/rat. Control animals were injected with the same volume of saline. Lung tissue and bronchoalveolar lavage (BAL) fluid were collected from rats on days 1, 3, and 7 after administration. In the group injected with TO1, total protein, cytokine-induced neutrophil chemoattractant (CINC)/growth-regulated gene product (GRO), interleukin (IL) 1beta, and tumor necrosis factor (TNF) alpha increased on day 1. Subsequently, total elastolytic activity and fucose levels in BAL increased by day 3. All parameters, except for fucose in BAL, recovered to the normal levels. Animals in the Ams group showed increased total protein and CINC/GRO and decreased total elastolytic activity in a dose-dependent manner on day 1. The fucose level increased on day 3 in the Ams group. All parameters returned to their control levels on day 7. Animals in the TOP group did not show significant changes any of parameters during the experimental period. Gene expression of TNF-alpha and monocyte chemoattractant protein (MCP) 3 in the lung increased dose-dependently in the animals treated with the three materials. The mRNAs for eotaxin and MIP-1alpha were overexpressed in the lung of animals treated with Ams and TO1, while RANTES mRNA was overexpressed dose-dependently in the lung of animals treated with Ams on day 1. Onset of inflammatory response was more rapid in the Ams group than the TO1 group. Recovery of the fucose level in BAL was slower in the TO1 group than in the Ams group, though we observed similar histopathological changes in the lung of animals with TO1 or Ams. We conclude that whisker-induced acute biological effects in the lung may be related to the shape of the whiskers and not to their chemical composition or surface crystal structure, showing biological effects similar to those of UICC amosite.
人造矿物纤维晶须的尺寸与某些种类的石棉相似。因此，这些矿物纤维引发了人们对职业环境中接触它们的工人潜在健康危害的担忧。本研究旨在确定气管内给予二氧化钛晶须（TO1）与非纤维状二氧化钛（TOP）和国际癌症研究机构（UICC）铁石棉（Ams）相比的急性生物学效应，以及它们与大鼠急性肺部炎症的关系。观察到的几何平均长度（微米）、宽度（微米）和几何标准差为：TO1（2.1[2.0]，0.14[1.53]）；Ams（4.3[3.3]，0.31[1.9]）；以及TOP（50纳米，1 - 2微米聚集体）。10周龄的Wistar - Jcl雄性大鼠以0.05至1.0毫克/只的剂量接受单次气管内注射受试材料。对照动物注射相同体积生理盐水。在给药后第1、3和7天从大鼠收集肺组织和支气管肺泡灌洗（BAL）液。在注射TO1的组中，第1天总蛋白水平、细胞因子诱导的中性粒细胞趋化因子（CINC）/生长调节基因产物（GRO）、白细胞介素（IL）1β和肿瘤坏死因子（TNF）α增加。随后，BAL中的总弹性蛋白酶活性和岩藻糖水平在第3天升高。除BAL中的岩藻糖外，所有参数均恢复到正常水平。Ams组动物在第1天总蛋白和CINC/GRO增加，总弹性蛋白酶活性呈剂量依赖性降低。Ams组岩藻糖水平在第3天升高。所有参数在第7天恢复到对照水平。TOP组动物在实验期间任何参数均未显示出显著变化。三种材料处理的动物肺中TNF - α和单核细胞趋化蛋白（MCP）3的基因表达呈剂量依赖性增加。嗜酸性粒细胞趋化因子和MIP - 1α的mRNA在Ams和TO1处理的动物肺中过度表达，而RANTES mRNA在第1天在Ams处理的动物肺中呈剂量依赖性过度表达。Ams组炎症反应的起始比TO1组更快。TO1组BAL中岩藻糖水平的恢复比Ams组更慢，尽管我们在TO1或Ams处理的动物肺中观察到了相似的组织病理学变化。我们得出结论，晶须诱导的肺部急性生物学效应可能与晶须的形状有关，而与其化学成分或表面晶体结构无关，显示出与UICC铁石棉相似的生物学效应。
