Induction of c-fos and c-jun proto-oncogenes in target cells of the lung and pleura by carcinogenic fibers.
Induction of c-fos and c-jun proto-oncogenes in target cells of the lung and pleura by carcinogenic fibers.
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DOI：
10.1165/ajrcmb.11.5.7946382
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发表时间：
1994-11
影响因子：
6.4
通讯作者：
Yvonne W. M. Janssen;N. Heintz;Joanne R Marsh;P. Borm;B. Mossman
中科院分区：
文献类型：
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作者：
Yvonne W. M. Janssen;N. Heintz;Joanne R Marsh;P. Borm;B. Mossman
为了研究石棉纤维和非石棉纤维对细胞增殖的作用机制，我们检测了石棉纤维和非石棉纤维对仓鼠气管上皮细胞（HTE）和大鼠胸膜间皮瘤细胞（RPM）中c-fos、c-jun和鸟氨酸脱羧酶（ODC）mRNA水平的影响。与青石棉相比，暴露于人造玻璃纤维-10（MMVF-10）或耐火陶瓷纤维-1（RCF-1）后，HTE细胞中c-jun mRNA的增加不那么引人注目。未检测到c-fos mRNA在HTE细胞暴露后的颗粒，但暴露HTE细胞H2 O2引起的c-fos和c-jun，ODC mRNA的增加之前的显着增加。ODC mRNA的增加也观察到在HTE细胞暴露于非石棉纤维后，而只有青石棉引起RPM细胞中ODC mRNA的升高。在RPM细胞中，青石棉和温石棉引起c-fos和c-jun mRNA水平的增加。在无毒浓度（≤ 5微克/平方厘米培养皿）下使用MMVF-10或RCF-1未观察到原癌基因诱导的增加。此外，毛沸石，一种纤维在人类间皮瘤的原因非常有效，造成更显着的海拔c-fos和c-jun. Nonfibrous颗粒（riebeckite，聚苯乙烯珠）没有改变原癌基因在这些细胞类型的表达，这表明颗粒的纤维几何形状是至关重要的诱导c-fos和c-jun。
To study mechanisms of cell proliferation by asbestos and nonasbestos fibers, we examined the effects of these agents on the mRNA levels of c-fos and c-jun and ornithine decarboxylase (ODC) in hamster tracheal epithelial (HTE) cells and rat pleural mesothelial (RPM) cells, the progenitor cells of bronchogenic carcinoma and mesothelioma, respectively. In comparison with crocidolite asbestos, increases in c-jun mRNA were less striking in HTE cells after exposure to man-made vitreous fiber-10 (MMVF-10) or refractory ceramic fiber-1 (RCF-1). No c-fos mRNA was detected in HTE cells after exposure to particulates, but exposure of HTE cells to H2O2 caused striking increases in c-fos and c-jun, which preceded increases in ODC mRNA. Increases in ODC mRNA were also observed in HTE cells after exposure to nonasbestos fibers, whereas only crocidolite asbestos caused elevations in ODC mRNA in RPM cells. In RPM cells, crocidolite and chrysotile asbestos caused increases in mRNA levels of both c-fos and c-jun. No increases in proto-oncogene induction were observed using MMVF-10 or RCF-1 at nontoxic concentrations (< or = 5 micrograms/cm2 dish). Moreover, erionite, a fiber extremely potent in the causation of mesothelioma in humans, caused more dramatic elevations in c-fos and c-jun. Nonfibrous particles (riebeckite, polystyrene beads) did not alter proto-oncogene expression in these cell types, suggesting that the fibrous geometry of particulates is critical in the induction of c-fos and c-jun.