STUDY OF SAFETY ASSESSMENT OF NEW MINERAL FIBERS USING MAKERS IN LUNG FIBROSIS-RELATED BIOLOGICAL DIAGNOSIS

利用制造商对肺纤维化相关生物诊断中的新型矿物纤维进行安全性评估的研究

• 批准号: 06680518
• 负责人: ISHIHARA Yoko
• 金额: $ 1.41万
• 依托单位: TOKYO WOMAN'S MEDICAL COLLEGE
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1994
• 资助国家: 日本
• 起止时间: 1994 至 1995
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06680518/
• 关键词: Asbestos; Asbestos substitute; Macrophages; cytotoxicity test; TNF-alpha; IL-beta; Ceramic fibers; Micro glass wool; ウィスカ-; サイトカイン; ヒト肺胞マクロファージ; 細胞毒性試験法; MIP-1α; IL-8; シリカ

We studied about usefulness of new method which measured lung fibrosis-related cytokines released from alveolar macropahges in safety evaluation of mineral fibers including asbestos substitute.(1) TNF-alpha, IL-beta, IL-8, MIP-1alpha and GRO released from human alveolar macrophages were increased by UICC amosite, crocidolite and chrysotile.(2) Co-culture of human fibrobrasts accelerated the increases of IL-1beta and GRO in human alvelar macrophages with asbestos.(3) On the basis of finding in human alveolar macrophage, we tested effects of three kind of ceramic fibers and micro glass wool including MMMF,three kind of whiskers, UICC crocidolite and tremolite on IL-1beta and TNF-alpha released from mouse macrophage-like cells.(4) In cytotoxicity test, all of these fibers in 1-10mug/ml showed no-effect and Sic whisker of 100mug-1mg/ml only revealed high cytotoxicity.(5) K-Ti-O- and TiO whiskers showed same effect, ceramic fiber group, micro glass wool and SiC whisker showed high sensitivity in MTT test when compared with UICC crocidolite.(6) Although TNF-alpha in cell culture medium increased by MMMF or whisker compared with UICC crocidolite, effect of ceramic fiber was bigger than that of whiskers.(7) Intracellular content of IL-1beta showed same level or a little increase in MMMF,and whisker revealed lower than that of UICC crocidolite.From these results, it suggested that measurements of TNF-alpha and IL-beta including lung fibrosis-related cytokines might be useful in safety evaluation of asbestos substitute. However, different finding between cytotoxicity test, MTT test, TNF-alpha and IL-beta required the comparison with in vivo and in vitro experiments in these asbestos substitutes.

我们研究了测量肺泡巨噬细胞释放的肺纤维化相关细胞因子的新方法在包括石棉替代品在内的矿物纤维的安全性评估中的有用性。(1)UICC铁石棉、青石棉和温石棉增加了人肺泡巨噬细胞释放的TNF-α、IL-β、IL-8、MIP-1α和GRO。(2) 人成纤维细胞与石棉的共培养加速了人肺泡巨噬细胞中IL-1β和GRO的增加。(3)在人肺泡巨噬细胞中发现的基础上，我们测试了MMMF、三种晶须、UICC青石棉和透闪石三种陶瓷纤维和微玻璃棉对IL-1β和GRO的影响。 小鼠巨噬细胞样细胞释放的TNF-α。(4)在细胞毒性测试中，1-10mug/ml的这些纤维均无作用，而100mug-1mg/ml的SiC晶须仅表现出较高的细胞毒性。(5)K-Ti-O-和TiO晶须表现出相同的效果，陶瓷纤维组、微玻璃棉和SiC晶须在 与UICC青石棉相比的MTT测试。(6)虽然与UICC青石棉相比，MMMF或晶须增加了细胞培养基中的TNF-α，但陶瓷纤维的影响大于晶须。(7)细胞内IL-1β含量与MMMF相同或略有增加，而晶须低于UICC青石棉。从这些结果来看， 这表明，TNF-α和IL-β（包括肺纤维化相关细胞因子）的测量可能有助于评估石棉替代品的安全性。然而，细胞毒性试验、MTT试验、TNF-α和IL-β之间的不同发现需要与这些石棉替代品的体内和体外实验进行比较。

项目成果

Y.Ishihara: "The measurment of chemokines and cell growth factor for safety evaluation of insoluble particle and fibers in celltoxicity test of target organs" J Occup.Health. 37. 513A (1995)

Y.Ishihara：“趋化因子和细胞生长因子的测量用于靶器官细胞毒性试验中不溶性颗粒和纤维的安全性评估”J Occup.Health。

Y. ISHIHARA: "Asbestos and silica particlas stimulated human alvealar macrophages and fibroblasts to release various cytokines" J Investigation Med.43. 365A (1995)

Y. ISHIHARA：“石棉和二氧化硅颗粒刺激人肺泡巨噬细胞和成纤维细胞释放各种细胞因子”J Investigation Med.43。

Y.Ishihara: "Accelaration and inhibition of nitric oxide production in macrophages stimulated by silica and asbestos" Experimental Biology. (in press). (1996)

Y.Ishihara：“二氧化硅和石棉刺激巨噬细胞中一氧化氮生成的加速和抑制”实验生物学。

Y. ISHIHARA: "Acceleration and Inhibition of nitric oxide production in macrophages stimulated by silica and ashestos" Experlmental Biology ‘96. (発表予定). (1996)

Y. ISHIHARA：“二氧化硅和灰烬刺激巨噬细胞中一氧化氮产生的加速和抑制”实验生物学96（即将发表）。

Y.ISHIHARA: "Ashestos and sillca perticles Atimulated human alveolar nacrophagcn and fihroblasts to nelease of variouas cytokine" J.Investigation Med.43. 365A- (1995)

Y.ISHIHARA：“Ashestos 和 silca perticles 刺激人肺泡噬菌体和成纤维细胞释放各种细胞因子”J.Investigation Med.43。