Effect of chrysotile asbestos and silica on the microsomal metabolism of benzo(a)pyrene

Our plain-English summary of Effect of chrysotile asbestos and silica on the microsomal metabolism of benzo(a)pyrene, by C. Kandaswami, P.J. O'Brien (Environmental Health Perspectives, 1983).

The study

• Authors: C. Kandaswami, P.J. O'Brien
• Journal: Environmental Health Perspectives
• Published: 1983;51:311-4
• Cited by: 6 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

The effects of chrysotile, water-leached chrysotile, and silica on microsomal metabolism of benzo(a)pyrene in vitro were studied. Examination of benzo(a)pyrene metabolites generated by 3-methylcholanthrene-pretreated rat liver microsomes, in the presence of chrysotile fibers, revealed a reduction in the overall metabolism of the hydrocarbon. Thus, chrysotile appeared to modify the activities of aryl hydrocarbon hydroxylase and epoxide hydrolase. Leaching chrysotile in deionized water for 24 hr elicited a similar response. Silica, in contrast to chrysotile, did not decrease the microsomal metabolism of benzo(a)pyrene. Chrysotile, as well as water-leached chrysotile, considerably diminished the microsomal production of water-soluble benzo(a)pyrene metabolites. Precoating the fibers with heparin or bovine serum albumin partially abolished this inhibition. The liver microsomal metabolism of benzo(a)pyrene in rats subjected to intraperitoneal administration of chrysotile was 58% of that in untreated rats.

In plain English

This laboratory study tested whether chrysotile asbestos changes how rat liver enzymes break down benzo(a)pyrene, a cancer-causing chemical. Liver preparations (microsomes) from rats pretreated with 3-methylcholanthrene were mixed for 1 hour with chrysotile, water-soaked chrysotile, or silica. Total breakdown of benzo(a)pyrene was 1.11 nmole per mg of protein per minute with no particles, 0.75 with chrysotile, 0.71 with water-soaked chrysotile and 1.25 with silica. Over a 30-minute incubation, chrysotile also reduced water-soluble breakdown products (9.86 versus 13.51 nmole per mg protein without particles; silica gave 13.68) and lowered another liver enzyme's activity. Coating the fibers with heparin or bovine serum albumin partly removed the effect. In two groups of three rats, chrysotile injected into the abdomen lowered liver microsomal aryl hydrocarbon hydroxylase activity to 58% of that in saline-injected rats (0.46 versus 0.79 nmole per mg protein per minute). The authors concluded that asbestos could inhibit benzo(a)pyrene metabolism in liver microsomes. They suggested this might contribute to asbestos acting as a cocarcinogen. They noted they had not shown that fibers reached the liver.

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: Laboratory (in vitro) experiments on rat liver microsomes, plus a small animal experiment with intraperitoneal injection of chrysotile
• Who was studied: Male Sprague-Dawley rats. Liver microsomes came from rats weighing 200-250 g that had been pretreated with 3-methylcholanthrene. The animal experiment used two groups of three rats weighing 125-150 g. The work was done at Memorial University of Newfoundland, Canada; the dates are not stated.
• Exposure: In the laboratory tests, microsomes were preincubated for 1 hour at 37 degrees C with 1.0 mg/mL of one of three materials: UICC standard reference Canadian chrysotile B, chrysotile leached in deionized water for 24 hours, or silica (80-120 mesh). In the animal experiment, each rat received 5.0 mg of chrysotile in 1.0 mL of sterile saline injected intraperitoneally, repeated after three days. The rats were killed after a further 5 days. Control rats received saline.
• Main results:
  • Organic-soluble benzo(a)pyrene metabolites were lower with chrysotile-pretreated microsomes than with controls, measured in nmole per mg protein during a 15-minute incubation: polar 0.90 vs 1.68, diols 0.52 vs 1.19, phenols 0.27 vs 0.63, quinones 0.21 vs 0.80.
  • Total benzo(a)pyrene metabolized, in nmole per mg protein per minute: no treatment 1.11, silica 1.25, chrysotile 0.75, water-leached chrysotile 0.71.
  • Water-soluble benzo(a)pyrene metabolites, in nmole per mg protein formed during a 30-minute incubation: no treatment 13.51, chrysotile 9.86, silica 13.68.
  • Precoating chrysotile with heparin or bovine serum albumin partially abolished its inhibitory effect. No figures were given.
  • Chrysotile pretreatment lowered ethoxyresorufin deethylase activity, given as percentage of fluorescence intensity. Control 72.0 (range 62-76); chrysotile-treated 40.0 (range 37-45). Each value is an average of four determinations.
  • In rats injected intraperitoneally with chrysotile, liver microsomal aryl hydrocarbon hydroxylase activity was 0.46 nmole of benzo(a)pyrene metabolites per mg protein per minute, compared with 0.79 in saline-injected rats, or 58% of control. Each group had three rats, and values are averages of duplicate determinations.
• The authors' conclusion: The authors concluded that asbestos could inhibit the total metabolism of benzo(a)pyrene in liver microsomes. They suggested that this interference might prolong the time the carcinogen stays in tissue. They also suggested it might be an important event in asbestos acting as a cocarcinogen, and that simple adsorption of the hydrocarbon onto fibers could not entirely explain the effect.
• Limitations the authors state:
  • The authors did not demonstrate that asbestos fibers were present in the livers of the injected rats. They framed the consequences as conditional on the inhibition being due to chrysotile.

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.

Related studies

• Effects of asbetos, iron oxide, silica, and carbon black on the microsomal availability of benzo[a]pyrene — J.R. Lakowicz, D.R. Bevan (1979)
• Presentation of benzo(a)pyrene to microsomal enzymes by asbestos fibers in the Salmonella/mammalian microsome mutagenicity test — K. Szyba, A. Lange (1983)
• Effects of asbestos on membrane transport and metabolism of benzo(a)pyrene — C. Kandaswami, P.J. O'Brien (1980)
• Effect of particulates on metabolism and mutagenicity of benzo[a]pyrene — D.R. Bevan, W.E. Manger (1985)
• Studies on in vitro chrysotile-pleural mesothelial cell interaction: morphological aspects and metabolism of benzo-3,4-pyrene — M.C. Jaurand, I. Bastie-Sigeac, et al. (1983)
• Effects of crocidolite and chrysotile asbestos on cellular uptake and metabolism of benzo(a)pyrene in hamster tracheal epithelial cells — B.T. Mossman, A. Eastman, et al. (1983)

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