Morimoto Yasuo, Hirohashi Masami, Kasai Takahiko, Oyabu Takako, Ogami Akira, Myojo Toshihiko, Murakami Masahiro, Nishi Ken-ichiro, Kadoya Chikara, Todoroki Motoi, Yamamoto Makoto, Kawai Kazuaki, Kasai Hiroshi, Tanaka Isamu
Department of Occupational Pneumology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, Kitakyushu, Japan.
Inhal Toxicol. 2009 Sep;21(11):898-905. doi: 10.1080/08958370802641938.
In order to evaluate the chronic effect of polymerized toner particles on the lung, inflammation- and fibrosis-related genes were analyzed and 8-hydroxydeoxyguanosine (8-OHdG) was examined by using the lung tissue of rats subjected to 24 months of toner inhalation exposure. Wistar female rats were divided into four groups (5 weeks old, 30 rats in each): the high concentration exposure group (16.3 +/- 0.6 mg/m(3)), the medium concentration exposure group (4.4 +/- 0.3 mg/m(3)), the low concentration exposure group (1.6 +/- 0.2 mg/m(3)), and the control group (clean air). The material used was black toner, and its aerodynamic diameter in the exposure chamber was 3.0 microm. The rats were exposed to the material for 24 months (6 hours/day, 5 days/week) and dissected after the exposure period. RNA was extracted from one lung and the gene expression related to inflammation and fibrosis. Matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase-2 (TIMP-2), and type I collagen were analyzed according to the ratio of each gene/beta-actin. Also, 8-OHdG level in the lung tissue was measured by HPLC with an electrochemical detector. Small fibrotic foci were found in the toner exposed groups; however, progressive or irreversible fibrosis was not found. The incidence of small fibrotic foci and cell aggregation increased in a dose-dependent manner. There were no significant differences of expression of MMP-2, TIMP-2, and type I collagen between the control group and each exposed group. Lung tumors did not develop in each group. A significant production of 8-OHdG was not observed in the toner exposed groups. In conclusion, toner produced by polymerization was not associated with evidence of carcinogenesis in this experiment.
为了评估聚合调色剂颗粒对肺部的慢性影响，利用吸入调色剂24个月的大鼠肺组织，分析了炎症和纤维化相关基因，并检测了8-羟基脱氧鸟苷（8-OHdG）。将Wistar雌性大鼠分为四组（5周龄，每组30只）：高浓度暴露组（16.3±0.6 mg/m³）、中浓度暴露组（4.4±0.3 mg/m³）、低浓度暴露组（1.6±0.2 mg/m³）和对照组（清洁空气）。使用的材料是黑色调色剂，其在暴露舱中的空气动力学直径为3.0微米。大鼠暴露于该材料24个月（每天6小时，每周5天），暴露期结束后进行解剖。从一侧肺中提取RNA，并分析与炎症和纤维化相关的基因表达。根据每个基因与β-肌动蛋白的比例分析基质金属蛋白酶-2（MMP-2）、金属蛋白酶组织抑制剂-2（TIMP-2）和I型胶原蛋白。此外，通过带有电化学检测器的高效液相色谱法测量肺组织中的8-OHdG水平。在调色剂暴露组中发现了小的纤维化病灶；然而，未发现进行性或不可逆的纤维化。小纤维化病灶和细胞聚集的发生率呈剂量依赖性增加。对照组与各暴露组之间MMP-2、TIMP-2和I型胶原蛋白的表达无显著差异。每组均未发生肺肿瘤。在调色剂暴露组中未观察到8-OHdG的显著产生。总之，在本实验中，聚合产生的调色剂与致癌证据无关。
