The effect of asbestos-associated metal ions on the binding of benzo(a)pyrene to macromolecules in vitro

Our plain-English summary of The effect of asbestos-associated metal ions on the binding of benzo(a)pyrene to macromolecules in vitro, by R. Thomson, T.A. Kilroe-Smith, I. Webster (Environmental Research, 1978).

The study

• Authors: R. Thomson, T.A. Kilroe-Smith, I. Webster
• Journal: Environmental Research
• Published: 1978;15(2):309-19
• Cited by: 15 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

In seeking an explanation for the high risk of malignancy in workers exposed to both asbestos and benzo(a)pyrene inhaled in cigarette smoke, experiments have been carried out to test the effect of asbestos-associated trace metals on the covalent binding of benzo(a)pyrene in vitro. Most of the metals tested—nickel, cadmium, chromium, zinc, manganese, and copper—caused an overall decrease in the binding of benzo(a)pyrene in microsomal incubations containing exogenous DNA. That this represented a reduction in the binding to DNA was confirmed in the cases of zinc, nickel, and chromium. Magnesium caused a very slight increase in binding, and ferrous and ferric ions, while reducing the binding to DNA, caused an increase in binding to some component of high molecular weight in the incubation mixtures, over a narrow concentration range. The significance of these findings is discussed in relation to the development of malignant disease associated with asbestos exposure.

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

In plain English

This was an in vitro laboratory study using rat liver microsomes. Male Wistar rats aged 12 to 18 months were injected with benzo(a)pyrene (BP) to induce the enzyme system. Washed liver microsomes were then incubated with tritium-labelled BP, NADPH and added thymus DNA, together with one of several asbestos-associated trace metal ions (nickel, cadmium, chromium, zinc, manganese, copper, magnesium, ferrous and ferric iron) at concentrations in the range of 1 to 100 micromole per assay. Unbound BP was removed by ether extraction, and DNA was separated by gel filtration. Most metals tested caused a concentration-dependent reduction in overall BP binding. Gel filtration confirmed reduced binding to DNA with zinc, nickel and chromium. With 10 micromole added, the decrease was 48.6% for zinc and 12.0% for nickel; the chromium figures in this copy of the table do not agree with each other and are not reported here. Magnesium appeared to cause a very slight increase at low concentrations, which the authors said was difficult to assess. Ferrous and ferric ions reduced binding to DNA but increased binding to a high molecular weight component over a narrow concentration range. The authors concluded that trace metals may play some part in BP binding to cellular macromolecules.

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 experiment (biochemical incubations with rat liver microsomes and, in one experiment, postmitochondrial supernatant)
• Who was studied: Liver microsomes prepared from male Wistar rats aged 12 to 18 months, weighing approximately 250 g; no human subjects
• Exposure: Asbestos-associated trace metal ions (nickel, cadmium, chromium, zinc, manganese, copper, magnesium, ferrous and ferric iron) added to incubations containing benzo(a)pyrene and DNA, at concentrations in the range 1 to 100 micromole per assay (printed as 'Fmole', OCR for micromole)
• Main results:
  • Most metals tested produced a concentration-dependent reduction in the overall binding of BP in the microsomal incubations containing added DNA
  • Gel filtration confirmed that zinc, nickel and chromium ions reduced binding of BP to DNA
  • With 10 micromole of zinc, radioactivity in the DNA-containing fractions fell by 48.6% compared with the control incubation
  • With 10 micromole of nickel, radioactivity in the DNA-containing fractions fell by 12.0% compared with the control incubation
  • Ferrous and ferric ions reduced BP binding to DNA but increased binding to a higher molecular weight soluble component
  • In incubations with postmitochondrial supernatant, ferric ions increased the high molecular weight component eluted in the first peak, with increased BP binding, over a narrow concentration range
  • Magnesium ions appeared to cause only a very slight increase in binding at low concentrations, an effect the authors described as difficult to assess
  • In control experiments, adding rat liver microsomes increased BP binding to DNA by 67%
  • Amino acid analysis showed no significant difference in amino acid content between control samples and ferric-ion incubations; total protein in the samples was 32 to 40% by weight
• The authors' conclusion: The authors concluded that trace metals may play some part in the binding of BP to cellular macromolecules and hence in its carcinogenicity, and that this may be of particular significance for people exposed to both BP and asbestos. They considered the iron effect of possible significance and said it lent support to an earlier suggestion that metals contaminating Cape crocidolite may be implicated in malignant neoplasia.
• Limitations the authors state:
  • The authors said the slight magnesium effect was difficult to assess, because magnesium content varied widely between individual microsomal pellets and because magnesium acts as a cofactor in BP metabolism
  • The identity of the high molecular weight iron-BP complex was inferred from gel filtration only and was stated as a possibility

Topics

Medical terms in this study, explained in our Lexicon: Asbestos Exposure.

Related studies

• Study of the cell-transforming ability of amosite and crocidolite asbestos and the ability to induce changes in the metabolism and macromolecular binding of benzo(a)pyrene in C3H10T1/2 cells — A. Poole, R.C. Brown, et al. (1983)
• 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)
• Presentation of benzo(a)pyrene to microsomal enzymes by asbestos fibers in the Salmonella/mammalian microsome mutagenicity test — K. Szyba, A. Lange (1983)
• 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 asbetos, iron oxide, silica, and carbon black on the microsomal availability of benzo[a]pyrene — J.R. Lakowicz, D.R. Bevan (1979)
• Effects of asbestos on membrane transport and metabolism of benzo(a)pyrene — C. Kandaswami, P.J. O'Brien (1980)

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