Journal Article

Induction of Micronuclei following Exposure to Methylene Di-phenyl Diisocyanate: Potential Genotoxic Metabolites

B. Z. Zhong and P. D. Siegel

in Toxicological Sciences

Volume 58, issue 1, pages 102-108
Published in print November 2000 | ISSN: 1096-6080
Published online November 2000 | e-ISSN: 1096-0929 | DOI: http://dx.doi.org/10.1093/toxsci/58.1.102
Induction of Micronuclei following Exposure to Methylene Di-phenyl Diisocyanate: Potential Genotoxic Metabolites

More Like This

Show all results sharing these subjects:

  • Medical Toxicology
  • Toxicology (Non-medical)

GO

Show Summary Details

Preview

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/m3 MDI aerosol for 1 h/week ×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.

Keywords: micronucleus; methylene di-phenyl diisocyanate; metabolites; Brown Norway rats; V79 cells

Journal Article.  5096 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

Full text: subscription required

How to subscribe Recommend to my Librarian

Users without a subscription are not able to see the full content. Please, subscribe or login to access all content.