Relationship Between 1-Chloro-2,4-Dinitrobenzene-Induced Cytoskeletal Perturbations and Cellular Glutathione

Details

• Personal Author:
  Chou I-N ; Leung M-F
• Description:
  Exposure of 3T3 cells to micromolar doses of 1-chloro-2,4-dinitrobenzene, a substrate for glutathione-S-transferase, resulted in a rapid depletion of total cellular glutathione accompanied by disassembly of microtubules as visualized by fluorescence microscopy. However, prolonged incubation resulted in cellular recovery from 1-chloro-2,4-dinitrobenzene insult as evidenced by a steady rise in total cellular glutathione accompanied by microtubule reassembly to their normal organization 5 hours after treatment. To evaluate the role of total cellular glutathione in modulating the 1chloro-2,4-dinitrobenzene-induced cytoskeletal perturbation, we used 1-chloro-2,4-dinitrobenzene and/or buthiomine sulfoximine, an effective irreversible inhibitor of glutathione synthesis, to manipulate cellular glutathione levels. Incubation of 3T3 cells with 2.5 micro M 1-chloro-2,4-dinitrobenzene and 250 micro M buthiomine sulfoximine for 5 hours resulted in a complete depletion of total cellular glutathione accompanied by essentially complete loss of microtubules and marked alterations in the density and distribution pattern of microfilaments. Buthionine sulfoximine enhanced markedly the extent and duration of cellular glutathione depletion and the severity of microtubule disruption of 3T3 cells over the level achieved by 1-chloro-2,4-dinitrobenzene treatment alone. Furthermore, buthiomine sulfoximine also prevented the restoration of cellular glutathione content and microtubule reassembly that normally were evident 5 hours after 1-chloro-2,4-dinitrobenzene treatment. Exposure of 3T3 cells to 50 micro M 2-cyclohexene-l-one, which depletes free glutathione by conjugation, resulted in a complete depletion of total cellular glutathione content without altering the microtubule organization. These results suggest that the total glutathione content may be important for cellular recovery from 1-chloro-2,4-dinitrobenzene-mediated cytoskeletal injuries, and that microtubule disassembly observed in 1-chloro-2,4-dinitrobenzenetreated cells probably results from depletion of cellular glutathione coupled with binding to tubulin and/or other microtubule components. [Description provided by NIOSH]
• Subjects:
  Occupational Health Safety Sulfhydryl Compounds Toxicology
• Keywords:
  Cell Biology Cellular Effects Cellular Function Thiols Toxic Effects
• ISSN:
  0742-2091
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Massachusetts ; OSHA Region 1
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  51-66
• Volume:
  5
• Issue:
  1
• NIOSHTIC Number:
  nn:20060068
• Citation:
  Cell Biol Toxicol 1989 Jan; 5(1):51-66
• Contact Point Address:
  Mun-fai Leung, Department of Microbiology, Boston University School of Medicine, Boston, MA 02118
• Federal Fiscal Year:
  1989
• Performing Organization:
  Boston University Medical Campus, Boston, Massachusetts
• Peer Reviewed:
  True
• Start Date:
  19870929
• Source Full Name:
  Cell Biology and Toxicology
• End Date:
  19890930
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:17f102e1d132a1a3b2d0b5c8e1910017ba291cd7b9cb7ade8c18e58a436882b46d85528ffaedf3019939a0388f1113e1a02bed109aa8883fa9aaff11ecd86d31
• Download URL:
  https://stacks.cdc.gov/view/cdc/224099/cdc_224099_DS1.pdf
• File Type:
  [PDF - 585.01 KB ]