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

Our plain-English summary of Increased 8-hydroxyguanine in DNA and its repair activity in hamster and rat lung after intratracheal instillation of crocidolite asbestos, by R. Yamaguchi, T. Hirano, Y. Ootsuyama, et al (Japanese Journal of Cancer Research, 1999).

The study

• Authors: R. Yamaguchi, T. Hirano, Y. Ootsuyama, S. Asami, Y. Tsurudome, S. Fukada, H. Yamato, T. Tsuda, I. Tanaka, H. Kasai
• Journal: Japanese Journal of Cancer Research
• Published: 1999;90(5):505-9
• Cited by: 25 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

In plain English

In this animal experiment, young male Syrian hamsters and Wistar rats (six per data point) each received a single dose of crocidolite asbestos, glass fibers, or saline placed directly into the windpipe (intratracheal instillation), usually 2 mg of fiber. Some rats received 0.5, 2 or 10 mg of crocidolite. The researchers measured a type of oxidative DNA damage, 8-hydroxyguanine (8-OH-Gua), in lung DNA, and the lungs' activity in repairing it. In hamsters, 8-OH-Gua rose significantly one day after crocidolite compared with saline, then declined gradually. Repair activity rose significantly at day 7 and returned to saline levels by day 9. Glass fibers caused no significant change in either measure in hamsters. In rats, 8-OH-Gua increased with crocidolite dose one day after instillation, but the increase was not significant after glass fibers. Seven days after 2 mg, repair activity was 2 times control in crocidolite-treated rats and 1.3 times in glass-fiber-treated rats. The authors used crocidolite as a positive and glass fibers as a negative control for cancer-causing potential. They concluded these short-term (9-day) tests will be useful for evaluating fiber carcinogenicity.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: animal experiment (single intratracheal instillation, with a time-course study in hamsters and rats and a dose study in rats)
• Who was studied: 9-week-old male Syrian hamsters and 9-week-old male Wistar rats, 6 animals per data point, killed 1, 3, 5, 7 and 9 days after instillation (dose study rats killed after 1 day)
• Exposure: single intratracheal instillation of saline or 2 mg of crocidolite (a UICC reference sample) or glass fibers in 0.2 ml saline; in the rat dose study, 0.5, 2 or 10 mg crocidolite or 2 mg glass fibers
• Main results:
  • Hamsters: 8-OH-Gua in lung DNA was significantly increased 1 day after crocidolite compared with saline (P<0.01), then decreased gradually
  • Hamsters: repair activity after crocidolite increased significantly at 7 days (P<0.05) and returned to the saline level at 9 days
  • Hamsters given glass fibers: the increase in 8-OH-Gua was not significant and repair activity did not significantly change
  • Rats: 1 day after instillation, 8-OH-Gua in lung DNA increased with crocidolite dose; the increase was not significant in rats given 2 mg glass fibers
  • Rats: 7 days after 2 mg, repair activity was 2 times control in crocidolite-treated rats and 1.3 times in glass-fiber-treated rats
• The authors' conclusion: The authors concluded that measuring 8-OH-Gua and its repair activity in short-term (9-day) animal experiments will be useful for evaluating the carcinogenicity of fibers

Topics

The National Library of Medicine indexes this study under subjects our site covers: Crocidolite.

Medical terms in this study, explained in our Lexicon: Crocidolite, Mineral Fiber.

Related studies

• Changes in DNA 8-hydroxyguanine levels, 8-hydroxyguanine repair activity, and hOGG1 and hMTH1 mRNA expression in human lung alveolar epithelial cells induced by crocidolite asbestos — H.N. Kim, Y. Morimoto, et al. (2001)
• Comparison of functional, biochemical, and morphometric alterations in the lungs of 4 rat strains and hamsters following repeated intratracheal instillation of crocidolite asbestos — D.J. Padilla-Carlin, D.L. Costa (2011)
• The production of TNF-alpha and IL-1-like activity by bronchoalveolar leucocytes after intratracheal instillation of crocidolite asbestos — X.Y. Li, D. Lamb, et al. (1993)
• Macrophage phagocytic activity and cell phagocytic capacity following intratracheal instillation of a comixture of asbestos fibers — I. Trosic, M. Matausic-Pisl, et al. (1995)
• Pulmonary response of hamsters to fibrous glass: chronic effects of repeated intratracheal instillation with or without benzo[a]pyrene — V.J. Feron, P.M. Scherrenberg, et al. (1985)
• Induction of 8-hydroxydeoxyguanosine by man made vitreous fibres and crocidolite asbestos administered intraperitoneally in rats — C. Schürkes, W. Brock, et al. (2004)

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