The dose-dependent effects of ingested chrysotile on DNA synthesis in the gastrointestinal tract, liver, and pancreas of the rat

Our plain-English summary of The dose-dependent effects of ingested chrysotile on DNA synthesis in the gastrointestinal tract, liver, and pancreas of the rat, by D.E. Amacher, A. Alarif, S.S. Epstein (Environmental Research, 1975).

The study

• Authors: D.E. Amacher, A. Alarif, S.S. Epstein
• Journal: Environmental Research
• Published: 1975;10(2):208-16
• Cited by: 17 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The effects of single oral administration of saline suspensions of chrysotile A to fasting male albino rats on DNA synthesis in the GI tract, pancreas, and liver were studied after a subsequent interval of 3 days. Incorporation of [3H]TdR was elevated in the whole stomach, duodenum, and jejunum following administration of chrysotile in the dose range of 5 to 100 mg/kg; incorporation in the liver was, however, reduced. There was no change in pancreatic and colonic [3H]TdR uptakes following administration of chrysotile. Preliminary data suggest that physicochemical alterations of chrysotile by gastric acid may influence its subsequent effects on DNA synthesis.

PubMed has no abstract for this study. This is the authors' abstract, copied from the article.

In plain English

In this animal experiment at Case Western Reserve University, Cleveland, adult male rats were fasted for 24 hours before and after dosing. Each treated rat was given one dose of UICC standard Rhodesian chrysotile A in saline by stomach tube: 0.5, 5.0, 25.0, 50.0 or 100.0 mg/kg. Control rats got saline only. Three days later the authors measured DNA synthesis, as uptake of radioactively labeled thymidine, in the stomach, duodenum, jejunum, colon, liver and pancreas. Compared with controls, uptake was significantly higher in the stomach after 5.0 and 25.0 mg/kg, in the duodenum after 25.0 and 50.0 mg/kg, and in the jejunum after 5.0, 25.0, 50.0 and 100.0 mg/kg. Colon and pancreas showed no significant difference at any dose. Liver uptake was significantly lower after 25.0 and 50.0 mg/kg. In preliminary test-tube work, acid binding rose in proportion to chrysotile concentration. The authors concluded the effect was limited and dose-dependent, with the most effective doses for the stomach, duodenum and jejunum in the 5 to 50 mg/kg range. They noted whole-organ measurement may be less sensitive.

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 oral dose of chrysotile in rats, with DNA synthesis measured 3 days later, plus preliminary test-tube (in vitro) experiments reacting chrysotile with hydrochloric acid
• Who was studied: Adult male Charles River CD rats at Case Western Reserve University School of Medicine, Cleveland, Ohio (received for publication 1974). Five treatment groups of five animals each, plus one saline control group of 10 animals. Animals were fasted 24 hours before and 24 hours after dosing. Fewer animals were analyzed after successful intravenous injection of the label (for example, 8 controls and 3 to 5 per dose group where legible).
• Exposure: UICC standard reference Rhodesian chrysotile A, washed and suspended in normal saline. Given once by gavage (stomach tube) at 0.5, 5.0, 25.0, 50.0 or 100.0 mg/kg. Animals were killed 72 hours later, 60 minutes after an injection of tritiated thymidine.
• Main results:
  • Stomach: thymidine incorporation was significantly higher than in concurrent controls after 5.0 mg/kg (p less than 0.002) and 25.0 mg/kg (p less than 0.02) chrysotile
  • Duodenum: incorporation was significantly higher than controls after 25.0 and 50.0 mg/kg chrysotile (p less than 0.02)
  • Jejunum: incorporation was significantly higher than controls after 5.0, 25.0, 50.0 and 100.0 mg/kg chrysotile (p less than 0.05, 0.02, 0.05 and 0.05, respectively)
  • Colon and pancreas: incorporation did not differ significantly from controls at any chrysotile dose
  • Liver (left lobe): incorporation was significantly lower than controls after 25.0 mg/kg (p less than 0.05) and 50.0 mg/kg (p less than 0.02). The authors suggested this may reflect less labeled thymidine being available because of high uptake in the stomach and small intestine.
  • In vitro: chrysotile suspensions bound hydrochloric acid in direct proportion to asbestos concentration over at least 2 hours
• The authors' conclusion: The authors concluded there was a limited dose-dependent effect of chrysotile A on thymidine incorporation in the gastrointestinal tract of the fasted rat three days after dosing. The most effective doses for the stomach, duodenum and jejunum were in the 5 to 50 mg/kg range. Their preliminary acid data suggest that changes to the fibers in the stomach may influence these effects.
• Limitations the authors state:
  • Thymidine incorporation was measured in whole organs, which may be less sensitive than examining only the lining (epithelial) cells
  • Slight changes in DNA synthesis are hard to detect in gut organs that already have high normal levels
  • Doses above 50 mg/kg may act by one day and so could have been missed at the 3-day time point

Topics

Medical terms in this study, explained in our Lexicon: Chrysotile.

Related studies

• Effects of ingested chrysotile on DNA synthesis in the gastrointestinal tract and liver of the rat — D.E. Amacher, A. Alarif, et al. (1974)
• Enhancement of benzo[a]pyrene mutagenicity by chrysotile asbestos in rat liver epithelial cells — B. Reiss, C. Tong, et al. (1983)
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• Asbestos fibers in human pulmonary and extrapulmonary tissues — J. Huang, N. Hisanaga, et al. (1988)
• Recovery of ingested asbestos fibers from the gastrointestinal lymph in rats — P. Sebastien, R. Masse, et al. (1980)
• Absence of mutagenic activity of three forms of asbestos in liver epithelial cells — B. Reiss, S. Solomon, et al. (1982)

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