Effect of chrysotile asbestos on cytochrome P-450-dependent monooxygenase and glutathione-S-transferase activities in rat lung

Our plain-English summary of Effect of chrysotile asbestos on cytochrome P-450-dependent monooxygenase and glutathione-S-transferase activities in rat lung, by Q. Rahman, S.G. Khan, S. Ali (Chemico-biological Interactions, 1990).

The study

• Authors: Q. Rahman, S.G. Khan, S. Ali
• Journal: Chemico-biological Interactions
• Published: 1990;75(3):305-13
• Cited by: 12 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The in vitro and in vivo effect of a carcinogenic variety of asbestos, chrysotile, both on xenobiotic metabolizing enzymes such as benzo[a]pyrene hydroxylase, epoxide hydrolase as well as glutathione-S-transferase activities and microsomal lipid peroxidation in rat lung were examined. The in vitro incubation of chrysotile with microsomes significantly adsorbed heme proteins, cytochrome P-450 and P-448 with the concomitant decrease in the dependent monooxygenase activities. The prolonged incubation of this mineral fibre with microsomes also resulted in the release of heme. It also led to the depletion in the activities of epoxide hydrolase and glutathione-S-transferase. However, it induced lipid peroxidation. When these in vitro effects were validated in vivo, the exposure to early stages produced similar alterations as observed in in vitro studies. However, reverse pattern in the alterations was observed after 90 days of exposure except in the case of lipid peroxidation which remained induced.

In plain English

This was a laboratory study in rats at the Industrial Toxicology Research Centre in Lucknow, India, using UICC standard reference chrysotile asbestos. The authors measured lung enzymes that process foreign chemicals (benzo[a]pyrene hydroxylase, epoxide hydrolase and glutathione-S-transferase) and lipid peroxidation, a form of damage to cell membranes. In test-tube experiments, chrysotile bound the lung proteins cytochrome P-450 and P-448 and released heme from them after 72 hours. It also lowered the activity of all three enzymes and increased lipid peroxidation. Female rats then had 5 mg of chrysotile placed into the windpipe, with six rats examined at each time point. In these rats, cytochrome P-450 first fell between days 1 and 16, then rose between days 90 and 290, reaching 45% above the level in control rats by day 290. Two of the enzymes followed the same pattern. Glutathione-S-transferase fell throughout, and lipid peroxidation stayed raised at every time point. The authors concluded these changes may play a role in the cancer response caused by the fibre. They called this a hypothesis needing further study.

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 combining in vitro (test-tube) studies of rat lung cell fractions with an in vivo study of rats followed over time after exposure
• Who was studied: Female albino rats from the colony of the Industrial Toxicology Research Centre, Lucknow, India. Six animals were used at each time point in the in vivo study. Some rats were pretreated with 3-methylcholanthrene (3-MC) for the cytochrome P-448 experiments.
• Exposure: UICC standard reference chrysotile. In vivo: 5 mg instilled into the trachea in 0.5 ml normal saline. In vitro: 1 mg dust per mg protein (adsorption and heme release) or 500 µg dust per mg protein (enzyme activity and lipid peroxidation). Titanium dioxide was used as an inert comparison dust.
• Main results:
  • In vitro, chrysotile adsorbed 15.84 ± 1.03 picomoles of cytochrome P-450 per mg chrysotile from microsomes of control rats. It adsorbed 25.6 ± 1.67 picomoles of cytochrome P-448 per mg chrysotile from microsomes of 3-MC-treated rats.
  • After 72 hours of incubation, chrysotile released 4.84 ± 0.59 picomoles heme per mg chrysotile from control microsomes and 10.50 ± 0.86 from 3-MC-treated microsomes.
  • In vitro benzo[a]pyrene hydroxylase activity fell from 11.60 to 7.42 pmol/min per mg protein in untreated-rat samples (P less than 0.01). It fell from 49.75 to 18.10 in 3-MC-treated samples (P less than 0.001).
  • In vitro epoxide hydrolase activity fell from 0.0350 to 0.0140 (change in O.D. per mg protein per h) in untreated-rat samples (P less than 0.001).
  • In vitro glutathione-S-transferase activity fell from 126.2 to 88.9 nmol/min per mg protein in untreated-rat samples, and from 202.6 to 130.0 in 3-MC-treated samples (P less than 0.001). Inhibition was greater in 3-MC-treated samples. Titanium dioxide made no difference compared with untreated controls.
  • In vitro, chrysotile incubated with microsomes induced lipid peroxidation. The induction was greater for NADPH-dependent enzymatic lipid peroxidation than for ferrous-dependent non-enzymatic lipid peroxidation.
  • In exposed rats, lung cytochrome P-450 decreased between days 1 and 16, then increased significantly between days 90 and 290. By day 290 it was 45% higher than in control rats (values in Fig. 1 are given as percent of control). Benzo[a]pyrene hydroxylase and epoxide hydrolase showed the same pattern.
  • In exposed rats, glutathione-S-transferase activity decreased continuously.
  • In exposed rats, enzymatic and non-enzymatic lipid peroxidation in lung microsomes was significantly increased at all time intervals.
• The authors' conclusion: The authors concluded that chrysotile-induced impairment of phase I and phase II metabolizing enzymes in the lung, together with increased lipid peroxidation, may play a role in the fibre-mediated carcinogenic response.
• Limitations the authors state:
  • The authors presented their proposed cancer mechanism as a hypothesis that needs further studies to support it.

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, Glutathione (GSH), Carcinogenic.

Related studies

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• Cytochrome P450-mediated pulmonary metabolism of carcinogens: regulation and cross-talk in lung carcinogenesis — S. Anttila, H. Raunio, et al. (2011)
• Genetic polymorphism for glutathione-S-transferase mu in asbestos cement workers — K. Jakobsson, A. Rannug, et al. (1994)
• Radiographic changes and lung function in relation to activity of the glutathione transferases theta and mu among asbestos cement workers — K. Jakobsson, A. Rannug, et al. (1995)
• Diminution in kerosene-mediated induction of drug metabolizing enzymes by asbestos in rat lungs — J.M. Arif, S.G. Khan, et al. (1992)

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