Forsterite exposure causes less oxidative DNA damage and lung injury than chrysotile exposure in rats

Our plain-English summary of Forsterite exposure causes less oxidative DNA damage and lung injury than chrysotile exposure in rats, by A. Takata, H. Yamauchi, T. Toya, et al (Inhalation Toxicology, 2009).

The study

• Authors: A. Takata, H. Yamauchi, T. Toya, M. Aminaka, Y. Shinohara, N. Kohyama, K. Yoshida
• Journal: Inhalation Toxicology
• Published: 2009;21(9):739-46
• Cited by: 4 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Chrysotile (CH) is a pathogenic waste building material that can potentially be rendered innocuous via conversion to forsterite (FO) by heating at high temperatures. We compared the ability of FO and CH to cause oxidative DNA damage and lung injury. A single 1-mg intratracheal dose of CH or FO was administered to rats. Significant changes were observed 3 to 7 days after CH injection in alveolar macrophages, neutrophils, eosinophils, lymphocytes, total protein, and lactate dehydrogenase. High concentrations of 8-hydroxy-29-deoxyguanosine (8-OHdG) were also observed in the macrophages, other infiltrating inflammatory cells, granulomas, and in bronchiolar and alveolar epithelial cells. The overexpression of 8-OHdG was limited to airway epithelial and inflammatory cells surrounding the fibrotic foci 540 days after injection, indicating that the inflammatory effects of CH were persistent yet decreased with time. Compared to the CH group, acute lung inflammation observed in the FO group was less apparent and exhibited no progressive fibrosing lesions. The expression of 8-OHdG was transient and weak in the bronchiolar epithelial cells as well as in the inflammatory cells, consistent with low concentrations of 8-OHdG observed in the lungs. These findings confirm that FO causes significantly less inflammation and oxidative DNA damage in the lungs than CH.

In plain English

This animal experiment in Japan compared chrysotile asbestos with forsterite. The forsterite was made by heating portions of the same chrysotile sample at 1000°C for one hour. Male Wistar rats received a single 1-mg dose of chrysotile or forsterite into the windpipe; controls received saline. Lungs were examined from day 3 to day 540. In the chrysotile group, neutrophil, eosinophil and lymphocyte counts in fluid washed from the lungs rose significantly on days 3 and 7, while macrophage counts fell. Lung scarring (interstitial fibrosis) was intense by day 540. Lung levels of 8-OHdG, a marker of oxidative DNA damage, were significantly higher than in controls throughout the study. They peaked on day 14 and were still about 5 times the control value on day 540. In the forsterite group, lung changes were mild and short-lived, with no progressive fibrosis. Its 8-OHdG differences from controls were slight and not statistically significant. No tumors were found in either group. The authors concluded that forsterite's harmful effects were far less than chrysotile's. They noted that the forsterite sample had far fewer long fibers, which could have contributed to the difference.

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: a single intratracheal (into the windpipe) dose in rats, with chrysotile, forsterite and saline-control groups followed over time
• Who was studied: Male Wistar rats, dosed at 10 weeks of age. Each animal group consisted of five rats. Groups were a chrysotile group, a forsterite group and a saline control group. Rats were dissected on days 3, 7, 14, 30, 90, 180, 360 and 540. Procedures were approved by the Animal Research Committee at the National Institute of Occupational Safety and Health, Japan.
• Exposure: A single 1-mg dose (in 0.5 ml saline) of chrysotile (grade AX, Cassiar Mining Corp., British Columbia, Canada; fibers under 250 µm long), or of forsterite. The forsterite was made by heating portions of that chrysotile at 1000°C for 1 hour; X-ray analysis found no residual chrysotile, and the forsterite sample contained a high level of enstatite (2:1 forsterite to enstatite). Controls received 0.5 ml sterile saline.
• Main results:
  • Chrysotile group: neutrophil, eosinophil and lymphocyte counts in lung washing fluid were significantly increased on days 3 and 7 compared with controls (p less than .01). Neutrophils stayed significantly elevated until day 30.
  • Chrysotile group: alveolar macrophage counts in lung washing fluid were significantly lower than in controls on day 3 (91.0 plus or minus 24.5, versus 172 plus or minus 11.1 in controls). The authors described injury to these macrophages that persisted and delayed cell count recovery.
  • Forsterite group: only a slight increase in neutrophil and eosinophil counts, and little or no injury to alveolar macrophages.
  • Chrysotile group: interstitial fibrosis was intense by day 540 and extended to the bronchioles, alveolar ducts and alveoli.
  • Forsterite group: lung lesions were transient and considerably less severe than in the chrysotile group. The progressive fibrosing lesions seen with chrysotile were not apparent at day 540.
  • No neoplastic (tumor) lesions were found in either the chrysotile or the forsterite group.
  • Chrysotile group: lung 8-OHdG concentrations were significantly higher than in controls for the entire period (p less than .001). The peak was 44.7 plus or minus 12.2 per 10^6 dG on day 14. On day 540 the level was 11.7 plus or minus 1.95 per 10^6 dG, approximately 5 times the control value of 2.08 plus or minus 0.40 (p less than .001).
  • Forsterite group: differences in lung 8-OHdG from controls were slight and not statistically significant over the whole observation period.
  • Forsterite group: 8-OHdG staining was considerably weaker and more transient than in the chrysotile group, and was not detected on day 540.
  • The forsterite sample had about 1/1000th as many fibers longer than 20 µm as the chrysotile sample.
• The authors' conclusion: The authors concluded that forsterite's harmful effects were far less than chrysotile's over the 540-day observation period in rats. They wrote that forsterite did not cause oxidative DNA injury, suggesting it is less carcinogenic than chrysotile. They also said heat conversion to forsterite is one promising technique for reducing asbestos toxicity, but that much more experimentation is needed.
• Limitations the authors state:
  • Only a limited number of studies have been done on forsterite, so the results cannot yet be checked against an established body of literature.
  • The low toxicity of forsterite may partly reflect the particular forsterite used, and differences in fiber size between the two samples could have contributed to the differences in biological activity.
  • The fibrous form of forsterite can vary with heating temperature and pulverization method, so forsterite made by other techniques needs to be evaluated.
  • Effects of intratracheal administration differ depending on the size or dosage of the fibers given.

Mines named here

Asbestos mines this study is about. Each mine's page says who ran it, when it worked, and what it produced.

• Cassiar mine, British Columbia

All asbestos mines

Topics

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

Medical terms in this study, explained in our Lexicon: Forsterite, Chrysotile, Alveolar Macrophage, Lactate Dehydrogenase (LDH), 8-OHdG, Macrophage, Granuloma, Inflammation.

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