Mesothelial cell proliferation and biopersistence of wollastonite and crocidolite asbestos fibers

Our plain-English summary of Mesothelial cell proliferation and biopersistence of wollastonite and crocidolite asbestos fibers, by J.L. Macdonald, A.B. Kane (Fundamental and Applied Toxicology, 1997).

The study

• Authors: J.L. Macdonald, A.B. Kane
• Journal: Fundamental and Applied Toxicology
• Published: 1997;38(2):173-83
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The mesothelial lining is a target for the fibrotic and carcinogenic effects of mineral fibers. Fiber geometry, dimensions, chemical composition, surface reactivity, and biopersistence at the target tissue have been proposed to contribute to these toxic endpoints. We established a dose-response relationship between the number of fibers delivered to the parietal peritoneal lining, inflammation, and mesothelial cell proliferation induced by intraperitoneal injection of crocidolite asbestos fibers in mice. Persistence of these inflammatory and proliferative responses depended on persistence of fibers at the target tissue. Intraperitoneal injection of wollastonite fibers induced an early inflammatory and proliferative response that subsided after 21 days. Approximately 50% of wollastonite fibers were recovered by bleach digestion after 21 days and only 2% were recovered after 6 months. In contrast, the number of fibers recovered from tissue digests had not declined 6 months after injection of crocidolite asbestos. These results support the hypothesis that biopersistent fibers cause persistent inflammation and chronic mesothelial cell proliferation.

In plain English

This was an animal experiment. The authors injected male mice in the abdominal (peritoneal) cavity with crocidolite asbestos, wollastonite (a calcium silicate mineral), or salt solution, and followed them from 3 days to 6 months, using three to five mice per treatment group. Both fibers caused early inflammation and growth of mesothelial cells, the cells lining the cavity, on the underside of the diaphragm. This early growth rose with the number of fibers deposited there. Wollastonite was less potent at the doses tested. The number of wollastonite fibers recovered from diaphragm tissue fell by 50% after 21 days, and after 6 months only 2% of the fibers deposited at 3 days were recovered. Wollastonite fiber surfaces showed etching within 3 days. The number of crocidolite fibers recovered rose after 21 days and then leveled off. Patches of mesothelial cell growth persisted for 6 months after crocidolite, with a labeling index (the share of cells dividing) of 2–6%, compared with 0.03–0.05% in salt-solution controls. The authors concluded that the results support the hypothesis that persisting crocidolite fibers lead to chronic inflammation and continued mesothelial cell proliferation.

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: mice injected intraperitoneally with fibers or with saline (controls)
• Who was studied: Male C57Bl/6 mice, 2 months old, three to five mice per treatment group, Brown University School of Medicine, Providence, Rhode Island
• Exposure: UICC crocidolite asbestos and NYAD 1250 wollastonite (a fine-particle grade of calcium metasilicate), injected into the peritoneal cavity. Crocidolite doses were printed as 20 mg, 200 mg and 1 mg, and wollastonite doses as 200 mg, 2 mg and 10 mg (see text problems). Saline-injected mice were the controls. Animals were examined from 3 days to 6 months after injection.
• Main results:
  • Three days after injection, mesothelial cell proliferation increased with the number of fibers deposited on the underside of the diaphragm, for both crocidolite and wollastonite
  • At the doses tested, wollastonite was less potent than crocidolite in inducing mesothelial cell proliferation at 3 days
  • The number of wollastonite fibers recovered from the diaphragm by bleach digestion decreased by 50% after 21 days
  • After 6 months, the wollastonite fibers recovered from the diaphragm were 2% of the number deposited there at 3 days. This was a fiber count from digested tissue, not a share of the injected dose.
  • The number of crocidolite fibers recovered from the diaphragm rose after 21 days and then leveled off after 56 days
  • Six months after crocidolite injection, focal areas of mesothelial cell proliferation had a labeling index of 2–6%, compared with 0.03–0.05% in saline-injected controls
  • At the highest wollastonite dose (printed as 10 mg), mesothelial cell proliferation was elevated at 21 days and then declined to background levels at 56 days
  • For crocidolite, a statistically significant increase in the number of cells recovered by peritoneal lavage (a sign of inflammation) was found at all doses after 56 days
  • Surface etching of wollastonite fibers recovered from the diaphragm was visible after 3 days. No change in surface or shape was seen in recovered crocidolite fibers.
• The authors' conclusion: The authors concluded that the results support the hypothesis that persistence of crocidolite asbestos fibers at sites of lymphatic drainage in the peritoneum leads to chronic inflammation and persistent mesothelial cell proliferation
• Limitations the authors state:
  • The authors described choosing doses that cause a biologic response without a bolus (clumping) effect as a major caveat of intraperitoneal injection studies. The highest wollastonite dose produced large fiber clumps.
  • The authors stated it is unknown whether wollastonite etching, breaking and dissolution occurred in the peritoneal fluid or inside macrophages
  • The authors noted that the mechanism of fiber persistence and clearance in the mesothelial lining may differ from that in the lungs

Topics

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

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, biopersistence, Wollastonite, Crocidolite, Carcinogenic, Mineral Fiber, Surface Reactivity, Dose-response relationship.

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