Effects of antioxidants on fiber mutagenesis

Our plain-English summary of Effects of antioxidants on fiber mutagenesis, by T.K. Hei, Z.Y. He, K. Suzuki (Carcinogenesis, 1995).

The study

• Authors: T.K. Hei, Z.Y. He, K. Suzuki
• Journal: Carcinogenesis
• Published: 1995;16(7):1573-8
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Recent studies from this laboratory have shown that asbestos fibers are mutagenic in cultured mammalian cells when assayed using a system that can detect multilocus deletions. Southern analysis of the induced mutants shows that the majority contain large deletions ranging in size from a few thousand to several million basepairs. In the present study, the effects of free radical scavenging enzymes on the cytotoxic and mutagenic potential of chrysotile fibers were examined using the human-hamster hybrid (AL) cells. Exponentially growing cells were treated with graded doses of fibers for a 24 h period either in the presence or absence of catalase, superoxide dismutase (SOD) or Tempol. Fiber-exposed cells were treated with the various enzymes either concurrently with the fiber or extended through the entire expression period. While the survival of AL cells treated with graded doses of chrysotile fibers with or without a concurrent treatment with SOD and catalase was not significantly different, the mutation yield at the S1 locus was significantly reduced in cells treated with these antioxidant enzymes. Furthermore, cells treated with the enzymes for a prolonged period were not better protected than those treated only during fiber treatment. The SOD mimic nitroxide, Tempol, had no effect on either the survival or mutagenic yield of chrysotile fibers. While SOD and catalase reduced the mutagenic potency of asbestos fibers in AL cells, they did not alter the molecular spectrum of fiber-induced mutagenesis. Our results indicate that antioxidant enzymes can protect cells against the genotoxic damages induced by chrysotile fibers, and are highly suggestive of the roles of oxyradicals in the fibrogenic and carcinogenic mechanisms of asbestos fibers.

In plain English

This was a laboratory experiment on cultured human-hamster hybrid (AL) cells, not people. The authors exposed the cells to UICC standard reference chrysotile fibers for 24 hours. Some cells also received the antioxidant enzymes superoxide dismutase (SOD) and catalase, or Tempol. They then measured cell survival and mutations. SOD and catalase had essentially no effect on the survival of fiber-treated cells. However, they significantly reduced chrysotile-induced mutations at the S1 locus. Keeping them in for the following week gave no extra protection. At the HGPRT locus, mutants induced by 20 micrograms per ml of chrysotile averaged above zero but did not differ significantly from background. At the S1 locus, Tempol did not significantly reduce fiber-induced mutations, and Tempol alone was slightly mutagenic. The enzymes did not change the kind of mutations: a significant proportion still involved large losses of human chromosome 11. The authors concluded that antioxidant enzymes can protect cells against chrysotile-induced genetic damage. They also concluded that the results are highly suggestive of a role for oxygen radicals in the fibrogenic and carcinogenic mechanisms of asbestos.

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) cell culture experiment
• Who was studied: Cultured human-hamster hybrid (AL) cells carrying a single human chromosome 11, studied at Columbia University, New York; no human subjects
• Exposure: UICC standard reference chrysotile fibers. The cells received graded doses for 24 hours, and a single dose of 20 micrograms per ml (4 micrograms per square cm) was used in the mutation tests. Some cells also received SOD (25 U/ml) plus catalase (10 micrograms per ml), or Tempol (250 micromolar, the maximum non-cytotoxic dose).
• Main results:
  • In fiber-treated AL cells, adding the antioxidants had essentially no effect on cell survival (clonogenic viability).
  • A single 20 micrograms per ml dose of chrysotile gave an induced S1 mutation yield printed as 82.6 plus or minus 7.3. The figure legend gives the units as induced mutants per 10^5 survivors. The leading character before the number appears to be scanning damage.
  • SOD and catalase caused no S1 mutants on their own. Their presence during fiber treatment significantly reduced the mutagenic potential of chrysotile fibers at the S1 locus.
  • Cells exposed to the enzymes for the full 1-week expression period had a mutagenic yield comparable to cells given the enzymes only during fiber treatment.
  • At the HGPRT locus, the average number of induced mutants in the 20 micrograms per ml chrysotile group was greater than zero but not significantly different from background. Adding the enzymes lowered mutation incidence on average, but this was not statistically significant.
  • At the S1 locus, Tempol was slightly mutagenic by itself. It did not significantly reduce the chrysotile-induced mutant fraction (P greater than 0.2).
  • Among S1 mutants induced by fibers alone, 14/33 (42%) had lost the Wilm's tumor marker and 11/33 (33%) the APO marker. Among mutants from fibers plus SOD/catalase, the figures were 3/17 and 4/17 respectively. No mutant in any group had lost the RAS gene.
  • The authors reported that the antioxidant enzymes did not reduce the size of the deletions in fiber-induced mutants.
• The authors' conclusion: The authors concluded that antioxidant enzymes can protect cells against genetic damage induced by chrysotile fibers. They also concluded that the results are highly suggestive of a role for oxygen radicals in the fibrogenic and carcinogenic mechanisms of asbestos fibers.
• Limitations the authors state:
  • Mutant yield was low in the fiber plus enzyme group, so the chance that an isolated mutant was a spontaneous one approached 2 in 5 clones. The lower deletion percentages in that group might therefore reflect spontaneous mutants.
  • Unlike other studies, this one found no survival benefit. The authors said this may reflect the much lower antioxidant doses used and a different measure of viability.

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, Superoxide, Damages, Fibrogenic, Carcinogenic.

Related studies

• Genotoxic mechanisms of asbestos fibers: role of extranuclear targets — A. Xu, X. Huang, et al. (2007)
• Biological effects of naturally occurring and man-made fibres: in vitro cytotoxicity and mutagenesis in mammalian cells — R. Okayasu, L. Wu, et al. (1999)
• Antioxidant defense mechanisms of human mesothelioma and lung adenocarcinoma cells — K. Järvinen, P. Pietarinen-Runtti, et al. (2000)
• Benzo[a]pyrene-enhanced mutagenesis by man-made mineral fibres in the lung of lamda-lacI transgenic rats — J. Topinka, P. Loli, et al. (2006)
• Induction of heme oxygenase in mammalian cells by mineral fibers: distinctive effect of reactive oxygen species — K. Suzuki, T.K. Hei (1996)
• Potential toxicity of nonregulated asbestiform minerals: balangeroite from the western Alps. Part 3: Depletion of antioxidant defenses — E. Gazzano, C. Riganti, et al. (2005)

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