期刊
TOXICOLOGICAL SCIENCES
卷 58, 期 1, 页码 102-108出版社
OXFORD UNIV PRESS
DOI: 10.1093/toxsci/58.1.102
关键词
micronucleus; methylene di-phenyl diisocyanate; metabolites; Brown Norway rats; V79 cells
类别
Methylene di-phenyl diisocyanate (MDI) is used to make polyurethane products. The predominant occupational disease attributed to diisocyanates, including MDI, is asthma; however, the potential for genotoxicity has also been of concern. Diisocyanates are very reactive compounds that can undergo nonenzymatic hydrolysis to form methylenedianiline (MDA), or react under physiological conditions with primary amines to form ureas and/or with thiols to form labile thiol acid esters. MDA is a carcinogen in animals and a suspected carcinogen in humans. Brown Norway rats (BNR) were exposed to either 7 or 113 mg/m(3) MDI aerosol for 1 h/week x 3 weeks and sacrificed 1 week later. Micronuclei (MN) formation was assessed from bone marrow polychromatic erythrocytes (PCE). A dose-dependent increase in the frequency of micronucleated polychromatic erythrocytes (MN-PCEs) was noted. In vitro exposure of Chinese hamster lung fibroblasts (V79) to MDA or MDI-thiol conjugates, but not to MDI, significantly increased the frequency of MN. MDI-thiol conjugate-exposed cell cultures did not have detectable levels of MDA. A significant increase in the number of V79 cells in metaphase, as well as the number of cells with precipitants within both the cytoplasm and nuclei, were noted in MDI-glutathione-exposed cultures. The results of this study indicate that MDI aerosol exposure can cause MN formation through either the hydrolysis of MDI to MDA or possibly the formation of thiol conjugates.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据