Reactive oxygen species, chromosome mutation, and cancer: possible role of clastogenic factors in carcinogenesis

Our plain-English summary of Reactive oxygen species, chromosome mutation, and cancer: possible role of clastogenic factors in carcinogenesis, by I. Emerit (Free Radical Biology & Medicine, 1994).

The study

• Author: I. Emerit
• Journal: Free Radical Biology & Medicine
• Published: 1994;16(1):99-109
• Type of article: Review
• Cited by: 257 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Superoxide radicals may induce genotoxic effects by indirect action mechanisms, implicating the formation of more long-lived, secondary clastogenic material called chromosome breakage factors or clastogenic factors (CF). CF are produced via the intermediacy of superoxide, and stimulate further superoxide production by competent cells. This results in a selfsustaining and longlasting process of clastogenesis, which may exceed the DNA repair system and ultimately lead to cancer. An increased cancer risk is indeed observed in conditions accompanied by CF formation. These include irradiated persons, asbestos workers, patients with chronic inflammatory diseases, HIV-infected persons, and the congenital breakage syndromes ataxia telangiectasia, Bloom's syndrome, and Fanconi's anemia. Because reactive oxygen species (ROS) are implicated in CF formation and CF action, antioxidants may be protective as anticlastogens and consequently as anticarcinogens. In persons at high risk because of their occupation, life style or place of residence, the presence of CF may represent an indication for chemoprevention of cancer by antioxidants. CF can be useful as biochemical markers and intermediate endpoints for the evaluation of promising drugs. They are therefore not only of interest as a mechanism by which ROS may exert genotoxic effects, but also have practical implications.

In plain English

This was a review article by a single author. It brought together earlier work, much of it from the author's own laboratory, on 'clastogenic factors' (CF). These are substances in blood plasma or cell-culture fluid that break chromosomes in healthy cells. The review covered irradiated people, chronic inflammatory diseases, HIV infection, three inherited chromosome-breakage syndromes, and cell cultures treated with chemicals that generate oxygen radicals. Asbestos appeared in that last group. The review reported that cultured mesothelial cells exposed to chrysotile fibers developed chromosome damage. Chromosome-breaking material was isolated from the culture fluid after the fibers had been filtered out, and the enzyme superoxide dismutase (SOD) suppressed its formation. The article body presented no data on asbestos workers themselves. As background, it noted that occupational asbestos exposure is associated with mesothelioma and bronchogenic carcinoma. The author proposed that CF sustain chromosome damage and may contribute to cancer, and described this as a hypothesis. The author concluded that CF are biomarkers of oxidative stress and could be used as intermediate markers in trials of antioxidants for cancer prevention.

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: Review article (narrative review of published and in-preparation work, largely from the author's laboratory)
• Who was studied: Studies of clastogenic factors in irradiated persons (including Chernobyl-exposed children and salvage workers), patients with chronic inflammatory diseases, HIV-infected persons, patients with ataxia telangiectasia, Bloom's syndrome and Fanconi's anemia, NZB mice, and cell cultures exposed to oxygen-radical-generating agents including asbestos
• Exposure: For asbestos: chrysotile fibers applied to cultured mesothelial cells. The cited paper's title refers to rat pleural mesothelial cells. Other exposures reviewed included ionizing radiation, the tumor promoter PMA, photosensitizers plus UVA light, and hypoxanthine plus xanthine oxidase.
• Main results:
  • In chrysotile-treated mesothelial cell cultures, chromosome-breaking material was found in the culture fluid after the fibers had been removed by ultrafiltration. The review attributed the effect to agents other than the fibers themselves.
  • Formation of clastogenic factor in the asbestos-treated cultures was suppressed by SOD, and less consistently by catalase.
  • Clastogenic factors were found in plasma of 14 of 19 children from the Chernobyl zone, and in 23 of 32 Armenian salvage workers (liquidators) sent to the Chernobyl reactor, compared with 2 of 41 unexposed controls.
  • Clastogenic activity was detected in all six Bloom's syndrome fibroblast strains tested, while normal fibroblast strains were negative.
  • In NZB mice aged 18 months, tumor frequency was 4 times higher in the high-breakage subline than in the low-breakage subline.
  • Plasma ultrafiltrates and cell-culture fluid from healthy persons were reported never to be clastogenic.
• The authors' conclusion: The author concluded that clastogenic factors are not specific to any disease but are biomarkers of oxidative stress, that antioxidants may act against them, and that they can be recommended as intermediate markers in cancer chemoprevention trials.
• Limitations the authors state:
  • The author presented the link between clastogenic factors and cancer as a hypothesis that the observed cancer rates favor.
  • The author noted that whether asbestos is a complete carcinogen or acts as a promoter is debated.
  • An earlier finding of a DNA-damaging factor from Bloom's syndrome fibroblasts could not be reproduced by several laboratories, including the author's own.
  • Whether oxygen radicals formed by the xanthine oxidase reaction play a role in carcinogenesis is not known.

Topics

Medical terms in this study, explained in our Lexicon: Reactive Oxygen Species (ROS), Carcinogenesis, Superoxide.

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