Increased 8-hydroxyguanine in DNA and its repair activity in hamster and rat lung after intratracheal instillation of crocidolite asbestos

Jpn J Cancer Res. 1999 May;90(5):505-9. doi: 10.1111/j.1349-7006.1999.tb00776.x.

Abstract

Asbestos and man-made-mineral fibers are known to increase one type of oxidative DNA damage, 8-hydroxyguanine (8-OH-(Gua), in vitro. In this study, we analyzed the 8-OH-Gua level in DNA and its repair activity after a single intratracheal instillation of fibers (crocidolite or glass) or saline to Syrian hamsters or Wistar rats. The 8-OH-Gua level was measured with a high-performance liquid chromatography-electrochemical detector (HPLC-ECD) system. The 8-OH-Gua repair enzyme activity was determined with an endonuclease nicking assay using a 32P-labeled or fluorescently labeled 22mer DNA that contains 8-OH-Gua at a specific position. A significant increase in the 8-OH-Gua level in the lung DNA was observed 1 day after the exposure to crocidolite, as compared to the saline control. The repair activity was increased significantly at 7 days. On the other hand, after exposure to glass fibers, little or no increase of these carcinogenicity indicators was detected. These assays of 8-OH-Gua and its repair activity in short-term animal experiments will be useful for evaluating the carcinogenicity of fibers. This is the first report of the increase of 8-OH-Gua and its repair activity in the animal lung after the instillation of asbestos fibers.

MeSH terms

  • Animals
  • Asbestos, Crocidolite / toxicity*
  • Carcinogens / toxicity*
  • Cricetinae
  • DNA / chemistry
  • DNA / drug effects*
  • DNA Repair*
  • Glass
  • Guanine / analogs & derivatives*
  • Guanine / analysis
  • Instillation, Drug
  • Intubation, Intratracheal
  • Lung / drug effects*
  • Lung / metabolism
  • Male
  • Mesocricetus
  • Rats
  • Rats, Wistar

Substances

  • Carcinogens
  • Asbestos, Crocidolite
  • 8-hydroxyguanine
  • Guanine
  • DNA