Modulation of genotoxic effects in asbestos-exposed primary human mesothelial cells by radical scavengers, metal chelators and a glutathione precursor

Our plain-English summary of Modulation of genotoxic effects in asbestos-exposed primary human mesothelial cells by radical scavengers, metal chelators and a glutathione precursor, by I. Poser, Q. Rahman, M. Lohani, et al (Mutation Research, 2004).

The study

• Authors: I. Poser, Q. Rahman, M. Lohani, S. Yadav, H.H. Becker, D.G. Weiss, D. Schiffmann, E. Dopp
• Journal: Mutation Research
• Published: 2004;559(1-2):19-27
• Cited by: 31 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

The genotoxicity of asbestos fibers is generally mediated by reactive oxygen species (ROS) and by insufficient antioxidant protection. To further elucidate which radicals are involved in asbestos-mediated genotoxicity and to which extent, we have carried out experiments with the metal chelators deferoxamine (DEF) and phytic acid (PA), and with the radical scavengers superoxide dismutase (SOD), dimethylthiourea (DMTU) and the glutathione precursor Nacystelyn trade mark (NAL). We investigated the influence of these compounds on the potency of crocidolite, an amphibole asbestos fiber with a high iron content (27%), and chrysotile, a serpentine asbestos fiber with a low iron content (2%), to induce micronuclei (MN) in human mesothelial cells (HMC) after an exposure time of 24-72 h. Our results show that the number of crocidolite-induced MN is significantly reduced after pretreatment of fibers with PA and DEF. This effect was not observed with chrysotile. In contrast, simultaneous treatment of cells with asbestos and the OH*scavenging DMTU or the O2- -scavenging SOD significantly decreased the number of MN induced by chrysotile and crocidolite. In particular, DMTU almost completely suppressed micronucleus induction by both fiber types. A similar effect was observed in the presence of the H(2)O(2)-scavenging NAL after chrysotile treatment of HMC. By means of kinetochore analysis, it could be shown that the number of clastogenic events is decreased after PA and DEF pretreatment of fibers as well as after application of the above-mentioned scavengers. Our results show that chrysotile asbestos induces an increased release of H(2)O(2) in contrast to crocidolite. Also, the iron content of the fiber plays an important role in radical formation, but nevertheless, chrysotile produces oxy radicals to a similar extent as crocidolite, probably by phagocytosis-mediated oxidative bursting.

In plain English

This was a laboratory study of human cells, not of people. The authors exposed mesothelial cells, taken from the ascites fluid of one non-cancerous patient in Rostock, Germany, to crocidolite or Rhodesian chrysotile asbestos for 24 to 72 hours. They counted micronuclei, small bodies of genetic material outside the main nucleus. Both fibers increased micronuclei: crocidolite up to 33 per 1000 cells and chrysotile up to 41 per 1000 cells, against 14 per 1000 in untreated cells. They then tested iron binders and scavengers of reactive oxygen molecules. Soaking crocidolite beforehand in the iron binders deferoxamine or phytic acid reduced micronuclei. Deferoxamine had no significant effect with chrysotile, and phytic acid had only a weak effect at 48 hours that became clearer at 72 hours. Dimethylthiourea brought micronucleus counts from both fibers down to the untreated level at 48 hours. Superoxide dismutase and Nacystelyn also reduced micronuclei at 48 hours. Most micronuclei contained chromosome fragments. The authors concluded that fiber iron plays a role in forming these reactive molecules but does not appear to be the only factor.

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 on cultured human cells
• Who was studied: Primary human mesothelial cells from the ascites fluid of one non-cancerous patient at the University Hospital, Rostock, Germany; cells from the first two passages were used
• Exposure: Crocidolite and Rhodesian chrysotile (UICC standard) at 0.5, 1.0, 5.0 and 10.0 micrograms per square centimetre for 24, 48, 66 and 72 hours. Fibers were either pretreated with the iron chelators deferoxamine (1, 5, 10 mM) or phytic acid (5 mM), or given together with superoxide dismutase (140 U/ml), dimethylthiourea (20 mM) or Nacystelyn (0.2 mM). Calcium sulfate was the negative control.
• Main results:
  • Crocidolite (0.5 to 1.0 micrograms per square centimetre, 72 hours) induced a maximum of 33 micronuclei per 1000 cells, compared with 14 per 1000 in controls (P < 0.001)
  • Chrysotile induced up to 41 micronuclei per 1000 cells after 1 microgram per square centimetre for 72 hours (P < 0.001)
  • At fiber concentrations above 5 micrograms per square centimetre, micronuclei decreased because of increased cell toxicity
  • Calcium sulfate (negative control) caused no increase in micronuclei
  • Pretreating crocidolite with deferoxamine (1, 5 and 10 mM) significantly decreased micronucleus induction
  • Deferoxamine had no significant influence on micronucleus induction by chrysotile
  • Phytic acid–pretreated crocidolite (1 to 5 micrograms per square centimetre, except 0.5) reduced micronuclei to control levels at 48 hours. The reduction was smaller at 72 hours and absent at 5 micrograms per square centimetre at 72 hours.
  • Phytic acid–pretreated chrysotile gave only a weak decrease at 48 hours. The decrease was more prominent at 72 hours, particularly at 1 microgram per square centimetre (P < 0.01).
  • Superoxide dismutase significantly (P < 0.001) reduced micronuclei from both fibers (1 microgram per square centimetre, 24 and 48 hours) almost to control levels. There was no significant reduction at 72 hours.
  • Dimethylthiourea given with either fiber (1 microgram per square centimetre, 48 hours) decreased micronucleus induction to the spontaneous rate of untreated cells
  • Nacystelyn with crocidolite significantly reduced micronuclei (P less than or equal to 0.001) almost to control level at 48 hours
  • Nacystelyn also significantly reduced micronuclei with chrysotile at 48 hours. No protective effect was seen at 72 hours.
  • Asbestos-induced micronuclei mainly contained chromosome fragments (70 to 74% kinetochore-negative)
• The authors' conclusion: The authors concluded that the iron content of the fiber plays a role in reactive oxygen species formation but does not appear to be the only factor in asbestos-mediated reactive oxygen species formation

Topics

The National Library of Medicine indexes this study under subjects our site covers: Chrysotile, Crocidolite.

Medical terms in this study, explained in our Lexicon: Mesothelial Cells, Glutathione (GSH), Genotoxicity, Reactive Oxygen Species (ROS), Superoxide, Crocidolite, Amphibole Asbestos, Chrysotile.

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