Elemental modifications and polycyclic aromatic hydrocarbon metabolism in human fibroblasts

Our plain-English summary of Elemental modifications and polycyclic aromatic hydrocarbon metabolism in human fibroblasts, by R.W. Hart, F.B. Daniel, O.R. Kindig, et al (Environmental Health Perspectives, 1980).

The study

• Authors: R.W. Hart, F.B. Daniel, O.R. Kindig, C.A. Beach, L.B. Joseph, R.C. Wells
• Journal: Environmental Health Perspectives
• Published: 1980;34:59-68
• Cited by: 13 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Mineral fibers and particulates represent one of the best documented, economically important, and ubiquitously occurring categories of human carcinogens. Yet, while a wealth of information exists concerning the mechanism of action of physical, chemical, and viral carcinogens, virtually nothing is known relative to the mechanism of action of this economically important class of carcinogenic compounds known as mineral fibers and particulates. While the length and diameter of various forms of asbestos have been associated with both cellular toxicity in vitro and tumor occurrence in vivo, nothing is known about whether or not these same physical properties are responsible for the purported synergistic interaction between cigarette smoking and asbestos exposure relative to the induction of bronchogenic carcinoma. Thus, while the risk of bronchogenic carcinoma for nonsmokers exposed to asbestos appears to be only slightly greater than that for unexposed nonsmoking populations, the risk of occurrence of this same tumor in asbestos workers who also smoke is approximately 100-fold greater than in nonsmoking asbestos workers. The risk of bronchogenic carcinoma is increased approximately 8-fold in asbestos workers who smoke over non-exposed smokers. Since it is clear that cigarette smoke contains over 150 polycyclic aromatic hydrocarbons, some of which are known animal carcinogens, and since other laboratories have reported that metals associated with asbestos redirect the metabolism of these agents, it was of interest to us to investigate the effects of mineral fibers on the metabolism and biochemistry of polycyclic aromatic hydrocarbons.

In plain English

This was a laboratory study using cultured human foreskin fibroblasts (skin cells), not people. The authors exposed the cells to three asbestos types (chrysotile, amosite and crocidolite) and used electron microscopy with X-ray analysis to compare the elements in fibers inside the cells with those in fibers outside. Within 24 hours, chrysotile changed least, with magnesium falling only slightly. Crocidolite lost about 10% of its magnesium and about 40% of its iron. Amosite showed lower iron but more magnesium. Chrysotile had no detectable effect on the breakdown of the hydrocarbon DMBA by rat liver enzymes. In the fibroblasts, binding of benzo(a)pyrene to DNA was 0.45 (micromoles per mole of deoxynucleotide) with benzo(a)pyrene alone, 0.48 when chrysotile was added at the same time, and 0.63 when chrysotile was added 24 hours earlier. Adding chrysotile first also increased cell killing. The authors concluded that chrysotile and benzo(a)pyrene had a synergistic effect on cell killing and DNA binding when chrysotile came first, and that this may not relate to elemental change in the fiber. They said it was premature to say which mechanism was responsible.

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) experiment in human cell cultures, using electron microscopy with X-ray microanalysis, rat liver microsome metabolism tests, DNA-binding measurements and cell survival (cytotoxicity) tests
• Who was studied: Human foreskin fibroblast cell cultures. For the fiber analysis, the authors examined several hundred cells and thousands of crystals for each fiber type. Microsomal tests used rat liver microsomes.
• Exposure: Chrysotile (NIEHS intermediate-sized), amosite and crocidolite fibers, alone or with the polycyclic aromatic hydrocarbons benzo(a)pyrene and 7,12-dimethylbenz(a)anthracene (DMBA). In the DNA-binding test, chrysotile was given at 1 microgram per ml and benzo(a)pyrene at 2 micromolar, either with no chrysotile, simultaneously, or 24 hours after chrysotile.
• Main results:
  • Chrysotile taken up by the cells showed the least change in elemental composition of the three fibers. Its magnesium fell only slightly 24 hours after treatment, and no other elemental change was seen.
  • Crocidolite inside the cells, compared with the standard, showed a slight reduction in magnesium (approximately 10%) and a large reduction in iron (approximately 40%).
  • Amosite inside the cells showed a significantly lower iron-to-silicon ratio than the standard.
  • Amosite inside the cells showed a higher magnesium level than the standard.
  • In rat liver microsome reactions, NIEHS chrysotile at concentrations as high as 2 mg/ml had no detectable effect on how much DMBA was metabolized or on the kind of metabolites formed.
  • Benzo(a)pyrene metabolite profiles in the fibroblasts were similar across treatments, except for early-eluting polar material. That material increased significantly when cells were given chrysotile 24 hours before the hydrocarbon.
  • Benzo(a)pyrene bound to fibroblast DNA at 0.45 micromoles per mole of deoxynucleotide with no chrysotile and 0.48 with chrysotile added at the same time, which the authors described as approximately equivalent.
  • When chrysotile was added 24 hours before benzo(a)pyrene, DNA binding rose to 0.63 micromoles per mole of deoxynucleotide, which the authors reported as a significant increase.
  • Giving chrysotile 24 hours before benzo(a)pyrene increased cell killing compared with benzo(a)pyrene alone or benzo(a)pyrene given together with chrysotile.
• The authors' conclusion: The authors concluded that chrysotile showed little if any elemental change after 24 hours inside the cells. Even so, chrysotile and benzo(a)pyrene had a synergistic effect on cytotoxicity and DNA binding when chrysotile was added 24 hours before the hydrocarbon, and this effect may not relate to elemental change in the fiber. They hypothesized that elemental loss from amosite and crocidolite might redirect hydrocarbon metabolism.
• Limitations the authors state:
  • The authors listed several possible mechanisms for the increased DNA binding with chrysotile but stated it would be premature to say which is most likely.

Topics

Medical terms in this study, explained in our Lexicon: Fibroblast, Mineral Fiber, Carcinogenic, Asbestos Exposure, Bronchogenic Carcinoma.

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