Determination of Polycyclic Aromatic Sulfur Heterocycles in Diesel Particulate Matter and Diesel Fuel by Gas Chromatography with Atomic Emission Detection

Details

• Personal Author:
  Gannett P ; Griffith B ; Leonard, Stephanie ; Martirosyan A ; Shi XL ; Strobl J
• Description:
  NSC3852 (5-nitroso-8-quinolinol) has cell differentiation and antiproliferative activity in human breast cancer cells in tissue culture and antitumor activity in mice bearing P388 and L1210 leukemic cells. We investigated the mechanism of NSC3852 action in MCF-7 human breast cancer cells using electron spin resonance (ESR). Reactive oxygen species (ROS) were detected in MCF-7 cell suspensions incubated with NSC3852 using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO). Formation of the DMPO-OH adduct was quenched by the addition of superoxide dismutase but not by catalase, and we concluded that superoxide was generated in the NSC3852-treated cells. The flavoprotein inhibitor diphenylene iodonium suppressed ROS production, providing evidence for the involvement of a flavin-dependent enzyme system in the ROS response to NSC3852. A biologically significant oxidative response to NSC3852 occurred in MCF-7 cells. An early marker of oxidative stress was a decrease in the [glutathione]/[glutathione disulfide] ratio 1 h after NSC3852 addition. Oxidative DNA damage, marked by the presence of 8-oxoguanine, and DNA-strand breakage occurred in cells exposed to NSC3852 for 24 h. Apoptosis peaked 48 h after exposure to NSC3852. Pretreatment with the glutathione precursor N-acetyl-l-cysteine (NAC) prevented DNA-strand breakage and apoptosis. Pretreatment with NAC also reversed NSC3852 decreases in E2F1, Myc, and phosphorylated retinoblastoma protein, indicative of redox-sensitive pathway(s) in MCF-7 cells during G(1) phase of the cell cycle. We conclude that ROS formation is involved in the apoptotic and cell differentiation responses to NSC3852 in MCF-7 cells. [Description provided by NIOSH]
• Subjects:
  Animals Cells, Cultured DNA Environmental Monitoring Laboratories Neoplasms Occupational Health Safety
• Keywords:
  Animal-studies Breast-cancer Cancer Cell-cultures Cell-differentiation DNA-damage Exposure-assessment Exposure-levels Laboratory-animals Tissue-culture Tumors

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• ISSN:
  0022-3565
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 3 ; Virginia ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  317
• Issue:
  2
• NIOSHTIC Number:
  nn:20030100
• Citation:
  J Pharmacol Exp Ther 2006 May; 317(2):546-552
• Contact Point Address:
  Dr. Jeannine S. Strobl, Edward Via Virginia College of Osteopathic Medicine, 2265 Kraft Drive, Blacksburg, VA 24060
• Email:
  jstrobl@vcom.vt.edu
• Federal Fiscal Year:
  2006
• NORA Priority Area:
  Research Tools and Approaches: Cancer Research Methods
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Pharmacology and Experimental Therapeutics
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:0e33e2571db72fdd30d39ac38f521ec03a00c7331322632ed47f39be8dbd0e7ca70297ce7d22f0e3cb3ed2ca574543f2458b1243f2e84823398d2b74d1feb89e
• Download URL:
  https://stacks.cdc.gov/view/cdc/190926/cdc_190926_DS1.pdf
• File Type:
  [PDF - 1.29 MB ]