Effect of asbestos fibers on aryl hydrocarbon hydroxylase and aminopyrine N-demethylase activities of rat liver microsomes

Our plain-English summary of Effect of asbestos fibers on aryl hydrocarbon hydroxylase and aminopyrine N-demethylase activities of rat liver microsomes, by C. Kandaswami, M. Rahimtula, P.J. O'Brien (Toxicology, 1986).

The study

• Authors: C. Kandaswami, M. Rahimtula, P.J. O'Brien
• Journal: Toxicology
• Published: 1986;38(1):119-32
• Cited by: 3 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Chrysotile asbestos fibers impair the activities of rat liver microsomal aryl hydrocarbon hydroxylase (AHH), aminopyrine (AP) N-demethylase and dimethylnitrosamine (DMN) demethylase in vitro. This inhibition is concentration-dependent. Preincubation of 3-methylcholanthrene (3-MC)-pretreated rat liver microsomes with chrysotile depresses the overall metabolism of [G-3H]benzo[a]pyrene (BaP). Various forms of asbestos employed inhibit AHH activity to the same extent. However, other types of asbestos are not as effective as chrysotile in diminishing AP demethylase activity. Chrysotile and crocidolite fibers are not found to significantly change the apparent Km of AHH activity, from 3-MC-pretreated rat liver microsomes, for BaP. Increasing the microsomal protein concentration partially abolishes the inhibition of AHH activity caused by chrysotile fibers. Inhibition of AP demethylase and AHH activities is attenuated by bovine serum albumin (BSA) or ferritin. Depression of AHH activity by crocidolite is significantly reversed by ferritin. Since polymers such as ferritin override enzyme inhibition by chrysotile as well as crocidolite, surface chemical groups of the fibers may be involved in enzyme modification.

In plain English

This was a laboratory study of rat liver enzymes, not a study of people. The authors pretreated male Sprague-Dawley rats with injections of the chemical 3-methylcholanthrene. They then isolated microsomes (a liver cell fraction) and mixed them with standard reference samples of chrysotile, crocidolite, anthophyllite and amosite asbestos. With 2.0 mg/ml of fiber for one hour, chrysotile lowered the activity of aryl hydrocarbon hydroxylase, an enzyme that processes benzo[a]pyrene, by 63%. Crocidolite had a similar effect, and anthophyllite and amosite lowered it by 61% and 58%. At 4.0 mg/ml, the fibers lowered aminopyrine demethylase activity by 38% (chrysotile), 25% (crocidolite), 10% (anthophyllite) and 18% (amosite). The inhibition grew with chrysotile dose. Chrysotile also reduced overall benzo[a]pyrene breakdown and dimethylnitrosamine demethylase activity. Adding more microsomal protein partly reversed chrysotile's inhibition of the hydroxylase. Bovine serum albumin or ferritin lessened the inhibition of both the hydroxylase and aminopyrine demethylase. The authors concluded that surface chemical groups of the fibers may be involved, that iron content did not appear to be the principal factor, and that the inhibition might not be due to the fibers binding benzo[a]pyrene.

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: In vitro laboratory experiment on rat liver microsomes (animal tissue study)
• Who was studied: Liver microsomes from male Sprague-Dawley rats weighing 125 to 150 g. Most had been pretreated with daily intraperitoneal injections of 3-methylcholanthrene (40 mg/kg) for 4 days. The dimethylnitrosamine and the Table III aminopyrine demethylase assays used microsomes from rats without pretreatment. Most results were means of 5 determinations.
• Exposure: Union Internationale Contre le Cancer (UICC) standard samples of chrysotile, crocidolite, anthophyllite and amosite asbestos, obtained from the National Research Institute of Occupational Diseases, Johannesburg. Microsomes were preincubated with the fibers, usually for 60 minutes at 37 degrees C, at concentrations from 100 micrograms/ml to 5.0 mg/ml.
• Main results:
  • Chrysotile at 2.0 mg/ml for 1 hour depressed aryl hydrocarbon hydroxylase (AHH) activity of 3-MC-pretreated microsomes by 63% compared with microsomes incubated without chrysotile. Crocidolite caused a similar decrease.
  • Anthophyllite and amosite impaired AHH activity by 61% and 58%, respectively.
  • At 4.0 mg/ml, chrysotile caused a 38% inhibition of aminopyrine (AP) demethylase activity of 3-MC-pretreated microsomes.
  • At the same concentration, crocidolite impaired AP demethylase activity by 25%.
  • At the same concentration, anthophyllite and amosite reduced AP demethylase activity by 10% and 18%, respectively.
  • Chrysotile reduced total benzo[a]pyrene metabolism by 3-MC-pretreated microsomes in a concentration-dependent way, with 56% inhibition at 600 micrograms/ml.
  • The relative pattern of benzo[a]pyrene metabolites did not shift significantly in the presence of chrysotile.
  • Chrysotile inhibited AHH activity by 29% at 0.5 mg/ml and by 52% at 1 mg/ml.
  • Chrysotile at 1.0 mg/ml depressed AP demethylase by only 23%.
  • At 5.0 mg/ml chrysotile, AP demethylase and dimethylnitrosamine (DMN) demethylase activities fell by 38% and 22%, respectively. These assays used microsomes from rats without pretreatment.
  • Neither chrysotile nor crocidolite significantly changed the apparent Km of AHH for benzo[a]pyrene: 5.0 (plus or minus 0.8) micromolar for untreated microsomes, 5.5 (plus or minus 1.2) for chrysotile and 5.7 (plus or minus 1.4) for crocidolite.
  • Preincubation with chrysotile lowered the apparent Vmax of AHH from 3.1 to 1.4 (units garbled in the scan).
  • At 1.0 mg microsomal protein, AHH activity of chrysotile-incubated microsomes was 39% of untreated. With 4 times as much protein it rose to 65%, a partial reversal of inhibition.
  • Chrysotile-preincubated microsomes kept 37% of untreated AHH activity. With bovine serum albumin (BSA, 10 mg/ml) present, activity was restored to 83% of control.
  • With ferritin (0.5 mg/ml) present, chrysotile-preincubated microsomes kept 70% of untreated AHH activity.
  • Crocidolite (2.0 mg/ml) depressed AHH activity by 68%.
  • The crocidolite inhibition of AHH was only 28% with ferritin present and 40% with BSA present.
  • Chrysotile caused a 37% diminution of AP demethylase activity, but only a 16% inhibition with BSA present.
  • No inhibition of AP demethylase by chrysotile was seen with ferritin present. BSA gave full protection against inactivation by crocidolite.
• The authors' conclusion: The authors concluded that surface chemical groups of the fibers may be involved in enzyme modification. They inferred that iron oxide content is not a principal factor, since anthophyllite and amosite inhibit AHH as effectively despite having practically no Fe2O3. They suggested the inhibition might not be due to fiber adsorption of benzo[a]pyrene and could instead reflect interaction of the fibers with microsomal membrane proteins.

Topics

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

Related studies

• Aryl hydrocarbon hydroxylase in asbestos workers — S.M. Naseem, P.V. Tishler, et al. (1978)
• Aryl hydrocarbon hydroxylase induction in mitogen-stimulated lymphocytes by benzanthracene or cigarette tars adsorbed to asbestos fibers — T.L. McLemore, W.T. Jenkins, et al. (1979)
• Presentation of benzo(a)pyrene to microsomal enzymes by asbestos fibers in the Salmonella/mammalian microsome mutagenicity test — K. Szyba, A. Lange (1983)
• The stimulatory effects of asbestos on NADPH-dependent lipid peroxidation in rat liver microsomes — M. Fontecave, D. Mansuy, et al. (1987)
• Benzo[a]pyrene uptake into rat liver microsomes: effects of adsorption of benzo[a]pyrene to asbestos and non-fibrous mineral particulates — J.R. Lakowicz, D.R. Bevan (1980)
• Lipid peroxidation in microsomes induced by crocidolite fibres — M. Gulumian, F. Sardianos, et al. (1983)

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