Effectiveness of serum megakaryocyte potentiating factor in evaluating the effects of chrysotile and its heated products on respiratory organs

Our plain-English summary of Effectiveness of serum megakaryocyte potentiating factor in evaluating the effects of chrysotile and its heated products on respiratory organs, by A. Takata, H. Yamauchi, T. Toya, et al (Toxicology and Applied Pharmacology, 2011).

The study

• Authors: A. Takata, H. Yamauchi, T. Toya, S. Miyamoto-Kohno, Y. Iwatatsu, I. Teranaka, M. Aminaka, K. Yamashita, N. Kohyama
• Journal: Toxicology and Applied Pharmacology
• Published: 2011;252(2):123-9
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Chrysotile (CH), the most common form of asbestos, is rendered less toxic by heating it at 1000°C and converting it to forsterite (FO-1000). However, further safety tests are needed to evaluate human health risk of these materials. It has been reported that serum concentrations of megakaryocyte potentiating factor N-ERC/mesothelin become elevated in patients with mesotheliomas caused by asbestos exposure. In this study, a single 2mg dose of CH or FO-1000 was intratracheally administered to rats. Within 180days after the administrations, serum N-ERC/mesothelin concentrations, levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in lung tissues and pathological changes in respiratory organs were determined. In the CH group, a significant increase in serum N-ERC/mesothelin concentrations was observed immediately after intratracheal administration, and the elevation lasted for 30days. In lung tissues, positive staining for 8-OHdG in bronchioles, alveolar epithelium, inflammatory cells, and granulomas was evidence of a marked DNA oxidative damage. Furthermore, measurements of 8-OHdG in lung tissues based on the HPLC-ECD method suggested that serum N-ERC/mesothelin concentrations tended to increase when there are significant DNA damages in lung tissues. In contrast, in the FO-1000 group, a marked rise in serum N-ERC/mesothelin concentrations occurred only in the early phase (1-7days) after intratracheal administration. Similarly, FO-1000 induced elevation of 8-OHdG in lung tissues was transient and modest compared with those of the CH-treated animals. In both the CH and FO-1000 groups, we observed significant correlations between serum N-ERC/mesothelin concentrations and lung 8-OHdG concentrations (r=0.559, p=0.001 for the CH group; r=0.516, p=0.01 for the FO-1000 group). In summary, we demonstrated the possibility of using serum N-ERC/mesothelin concentrations as a useful biomarker for early phase exposure to either CH or FO-1000.

Copyright © 2010 Elsevier Inc. All rights reserved.

In plain English

In this animal experiment from Japan, the authors put a single 2 mg dose of chrysotile asbestos, or of forsterite made by heating that chrysotile at 1000 °C (FO-1000), into the windpipes of male rats. Control rats received salt water. Over 180 days they measured a blood protein, N-ERC/mesothelin, a marker of oxidative DNA damage (8-OHdG) in the lungs, and changes in lung tissue. Chrysotile caused inflammation, granulomas and, from day 30, interstitial fibrosis. Forsterite caused milder, transient inflammation and no obvious fibrosis at day 180. Neither group showed lesions of the visceral pleura or overgrowth of mesothelial cells. The blood protein rose in both groups from day 1. It stayed high until day 14 with chrysotile and fell faster with forsterite, and both groups were near control levels by day 180. Blood and lung measures were significantly correlated (chrysotile r=0.559; forsterite r=0.516). The authors concluded the blood protein may be useful as an early-phase marker of both materials' effects on the respiratory organs. They noted the six-month observation was short and cancer-causing properties were not examined.

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 dose in rats, with groups examined at time points up to 180 days
• Who was studied: Male Wistar rats, 10 weeks old at dosing, five per animal group, in three treatment arms (chrysotile, FO-1000, saline control), studied at a Japanese institute; Figure 5 gives n=30 for each of the chrysotile and FO-1000 groups
• Exposure: A single 2.0 mg dose in 1.0 ml saline of either chrysotile (grade AX, Cassiar Mining Corp., British Columbia, Canada; fibers under 250 μm long) or FO-1000, a forsterite made by heating that chrysotile at 1000 °C for 3 hours. FO-1000 had shorter fibrous particles and none 20 μm or longer.
• Main results:
  • Chrysotile group: interstitial fibrosis developed from day 30 onward
  • FO-1000 group: inflammation was modest and transient; at day 180 there was no obvious inflammation or pulmonary fibrosis
  • Both groups: no lesions of the visceral pleura and no hyperplastic mesothelial cells were seen
  • Both groups: serum N-ERC/mesothelin rose compared with controls from the first day after dosing (p less than 0.01)
  • Chrysotile group: serum N-ERC/mesothelin stayed high until day 14, then gradually declined
  • FO-1000 group: serum N-ERC/mesothelin was significantly lower than in the chrysotile group at days 7, 14 and 30
  • Both groups: serum N-ERC/mesothelin returned to nearly control levels by day 180
  • Chrysotile group: lung 8-OHdG was still higher than in controls at day 180
  • FO-1000 group: at day 180, lung 8-OHdG did not differ significantly from controls
  • Chrysotile group: serum N-ERC/mesothelin and lung 8-OHdG were significantly correlated (r=0.559, p=0.001)
  • FO-1000 group: a similar positive correlation was found (r=0.516, p=0.01)
• The authors' conclusion: The authors concluded that serum N-ERC/mesothelin may be useful as an early-phase biomarker for effects of chrysotile and FO-1000 on the respiratory organs. They also stated that appropriate exposure-preventing measures are required for workers handling both materials.
• Limitations the authors state:
  • The six-month observation period was short, and cancer-causing properties were not examined
  • How N-ERC/mesothelin enters the bloodstream is unclear

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: Chrysotile, Forsterite, Mesothelin, Mesothelioma, Asbestos Exposure, 8-OHdG, Epithelium, Granuloma.

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