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. 1997 Sep;105(Suppl 5):1109–1112. doi: 10.1289/ehp.97105s51109

Mechanism of asbestos-mediated DNA damage: role of heme and heme proteins.

Q Rahman 1, N Mahmood 1, S G Khan 1, J M Arif 1, M Athar 1
PMCID: PMC1470167  PMID: 9400708

Abstract

Several observations, including studies from this laboratory, demonstrate that asbestos generates free radicals in the biological system that may play a role in the manifestation of asbestos-related cytotoxicity and carcinogenicity. It has also been demonstrated that iron associated with asbestos plays an important role in the asbestos-mediated generation of reactive oxygen species. Exposure to asbestos leads to degradation of heme proteins such as cytochrome P450-releasing heme in cytosol. Our simulation experiments in the presence of heme show that such asbestos-released heme may increase lipid peroxidation and can cause DNA damage. Further, heme and horseradish peroxidase (HRP) can cause extensive DNA damage in the presence of asbestos and hydrogen peroxide/organic peroxide/hydroperoxides. HRP catalyzes oxidation reactions in a manner similar to that of prostaglandin H synthetase. Iron released from asbestos is only partially responsible for DNA damage. However, our studies indicate that DNA damage mediated by asbestos in vivo may be caused by a combination of effects such as the release and participation of iron, heme, and heme moiety of prostaglandin H synthetase in free radical generation from peroxides and hydroperoxides.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adachi S., Kawamura K., Yoshida S., Takemoto K. Oxidative damage on DNA induced by asbestos and man-made fibers in vitro. Int Arch Occup Environ Health. 1992;63(8):553–557. doi: 10.1007/BF00386345. [DOI] [PubMed] [Google Scholar]
  2. Gutteridge J. M., Wilkins S. Copper salt-dependent hydroxyl radical formation. Damage to proteins acting as antioxidants. Biochim Biophys Acta. 1983 Aug 23;759(1-2):38–41. doi: 10.1016/0304-4165(83)90186-1. [DOI] [PubMed] [Google Scholar]
  3. Hatch G. E., Gardner D. E., Menzel D. B. Stimulation of oxidant production in alveolar macrophages by pollutant and latex particles. Environ Res. 1980 Oct;23(1):121–136. doi: 10.1016/0013-9351(80)90099-7. [DOI] [PubMed] [Google Scholar]
  4. Jaurand M. C., Kheuang L., Magne L., Bignon J. Chromosomal changes induced by chrysotile fibres or benzo-3,4-pyrene in rat pleural mesothelial cells. Mutat Res. 1986 Mar;169(3):141–148. doi: 10.1016/0165-1218(86)90093-5. [DOI] [PubMed] [Google Scholar]
  5. Kamp D. W., Graceffa P., Pryor W. A., Weitzman S. A. The role of free radicals in asbestos-induced diseases. Free Radic Biol Med. 1992;12(4):293–315. doi: 10.1016/0891-5849(92)90117-y. [DOI] [PubMed] [Google Scholar]
  6. Lechner J. F., Tokiwa T., LaVeck M., Benedict W. F., Banks-Schlegel S., Yeager H., Jr, Banerjee A., Harris C. C. Asbestos-associated chromosomal changes in human mesothelial cells. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3884–3888. doi: 10.1073/pnas.82.11.3884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Lund L. G., Aust A. E. Iron mobilization from crocidolite asbestos greatly enhances crocidolite-dependent formation of DNA single-strand breaks in phi X174 RFI DNA. Carcinogenesis. 1992 Apr;13(4):637–642. doi: 10.1093/carcin/13.4.637. [DOI] [PubMed] [Google Scholar]
  8. Mahmood N., Khan S. G., Athar M., Rahman Q. Differential role of hydrogen peroxide and organic peroxides in augmenting asbestos-mediated DNA damage: implications for asbestos induced carcinogenesis. Biochem Biophys Res Commun. 1994 Apr 29;200(2):687–694. doi: 10.1006/bbrc.1994.1505. [DOI] [PubMed] [Google Scholar]
  9. Mossman B. T., Gee J. B. Asbestos-related diseases. N Engl J Med. 1989 Jun 29;320(26):1721–1730. doi: 10.1056/NEJM198906293202604. [DOI] [PubMed] [Google Scholar]
  10. Rahman Q., Khan S. G., Ali S. Effect of chrysotile asbestos on cytochrome P-450-dependent monooxygenase and glutathione-S-transferase activities in rat lung. Chem Biol Interact. 1990;75(3):305–313. doi: 10.1016/0009-2797(90)90073-v. [DOI] [PubMed] [Google Scholar]
  11. Takeuchi T., Morimoto K. Crocidolite asbestos increased 8-hydroxydeoxyguanosine levels in cellular DNA of a human promyelocytic leukemia cell line, HL60. Carcinogenesis. 1994 Apr;15(4):635–639. doi: 10.1093/carcin/15.4.635. [DOI] [PubMed] [Google Scholar]

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