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Mitochondrial DNA Damage during Mitochondrial Lipid Peroxidation

  • Andrew M. Hruszkewycz

Abstract

It is well known that the carcinogenic potency of radiation and chemical carcinogens is closely correlated with the induction of DNA damage (1–3); however, the ultimate mechanisms involved are far from clear. In the case of high energy radiation, generation of hydroxyl radicals (OH·) probably plays a key role, either by direct attack of OH· on DNA, or indirectly via initiation of lipid peroxidation (4,5). Initiation of lipid peroxidation may also be a consequence of the generation of oxygen centered radicals in the oxidative stress associated with metabolism of some chemical carcinogens(6). Thus lipid peroxidation may be one of the mechanisms linking both radiation and metabolism of chemical carcinogens to DNA damage. This view is supported by reports (7–12) that products of lipid peroxidation can cause DNA damage in model systems and mutations in prokaryotes. However, actual data showing DNA damage to eukaryotic genes by lipid peroxidation is limited and indirect (5,13). In this communication, evidence is reported showing extensive damage to DNA of liver mitochondria occurring concomitantly with mitochondrial lipid peroxidation. Mitochondrial rather than nuclear DNA was studied since the former exists as a discrete circular molecule of single molecular weight, which facilitates detection of small degrees of DNA damage. The study of the relationship between lipid peroxidation and DNA damage in mitochondria is important in the assessment of the carcinogenic potency of oxidative stress, especially since many strong carcinogenic agents preferentially attack mitochondrial DNA (14).

Keywords

Lipid Peroxidation Chemical Carcinogen Malonic Dialdehyde High Energy Radiation Carcinogenic Potency 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    D. Grunberger and R.M. Santella, Conformational changes in DNA induced by chemical carcinogens. In Genes and Proteins in Oncogenesis (I. B. Weinstein and H. J. Vogel, Eds.) pp. 13–40. Academic Press, New York (1983).Google Scholar
  2. 2.
    I. Emerit and P. Cerutti, Icosanoids and chromosome damage. In Icosanoids and Cancer (H. Thaler-Dao, A. Crastes de Paulet and R. Paoletti, Eds.) pp. 127–138. Raven Press, New York (1984).Google Scholar
  3. 3.
    R. L. Willson, Iron and hydroxyl free radicals in enzyme inactivation and cancer. In Free Radicals, Lipid Peroxidation and Cancer (D.C.H. McBrien and T.F. Slater, Eds.) pp. 275–303. Academic Press, New York (1982).Google Scholar
  4. 4.
    M.G. Simic and S.V. Jovanovic, Free radical mechanisms of DNA base damage. In Mechanisms of DNA Damage and Repair (M.G. Simic, L. Grossman and A.C. Upton, Eds.) pp. 39–49. Plenum Press, New York (1986).Google Scholar
  5. 5.
    B.N. Ames and R.L. Saul, Oxidative DNA damage as related to cancer and aging. Prog. Clin. Biol. Res. 209A, 11–26 (1986).PubMedGoogle Scholar
  6. 6.
    P.A. Cerutti, Prooxidant states and tumor promotion. Science 227, 375–381 (1985).PubMedCrossRefGoogle Scholar
  7. 7.
    U. Reiss and A.L. Tappel, Fluorescent product formation and changes in structure of DNA reacted with peroxidizing arachidonic acid. Lipids J, 199–202 (1973).Google Scholar
  8. 8.
    S. Yonei and H. Furui, Lethal and mutagenic effects of malondialdehyde, a decomposition product of peroxidized lipids, on Escherichia coli with different DNA-repair capacities. Mutation Res. 23–32 (1981).Google Scholar
  9. 9.
    F. H. Mukai and B.D. Goldstein, Mutagenicity of malonaldehyde, a decomposition product of peroxidized polyunsaturated fatty acids. Science 191, 868–869 (1976).PubMedCrossRefGoogle Scholar
  10. 10.
    U.M. Marinari, M. Ferro, L. Sciaba, R. Finollo, A.M. Bassi and G. Brambilla, DNA-damaging activity of biotic and xenobiotic aldehydes in Chinese hamster ovary cells. Cell Biochem. and Func. 2, 243–248 (1984).CrossRefGoogle Scholar
  11. 11.
    L. J. Marnet, H.K. Hurd, M.C. Hollstein, D.E. Levin, H. Esterbauer and B.N. Ames, Naturally occurring carbonyl compounds are mutagens in Salmonella tester strain TA 104. Mutation Res. 148, 25–34 (1985).CrossRefGoogle Scholar
  12. 12.
    S. Alaska, Inactivation of transforming activity of plasmid DNA by lipid peroxidation. Biochim. Biophys. Acta, 867, 201–208 (1986).Google Scholar
  13. 13.
    I. Emerit, S.H. Khan and P.A. Cerutti, Treatment of lymphocyte cultures with a hypoxanthine-xanthine oxidase system induces the formation of transferable clastogenic material. J. Free Rad. Biol. Med. U 51–57 (1985).Google Scholar
  14. 14.
    B.G. Niranjan, N.K. Bhat, and N.G. Avadhani, Preferential attack of mitochondrial DNA by aflatoxin B during hepatocarcinogenesis. Science 215, 73–75 (1985).CrossRefGoogle Scholar
  15. 15.
    A.K. Ghoshal and R.O. Recknagel, Positive evidence of acceleration of lipoperoxidation in rat liver by carbon tetrachloride: In vitro experiments. Life Sci. 4 1521–1530 (1965).PubMedCrossRefGoogle Scholar
  16. 16.
    O.H. Lowry, N.J. Rosebrough, A.L. Farr and R.J. Randall, Protein measurement with the folin phenol reagent. J. of Biol. Chem. 193, 265–275 (1951).Google Scholar
  17. 17.
    T.K. Palva and E.J. Palva, Rapid isolation of animal mitochondrial DNA by alkaline extraction. FEBS Letters 192, 267–170 (1985).PubMedCrossRefGoogle Scholar
  18. 18.
    R. Wilkinson, A. Hawks, and A.E. Peggy, Methylation of rat liver mitochondrial deoxyribonucleic acid by chemical carcinogens and associated alterations in physical properties. Chem.-Biol. Interactions 9, 157–167 (1975).CrossRefGoogle Scholar
  19. J. F. Francisco, F.F. Vissering and M.V. Simpson, Two aspects of mitochondrial DNA structure: The occurrence of two types of mitochondrial DNA in rat liver and the isolation from rat liver of DNA complexes of high buoyant density. In Mitochondria 1977 (W. Bendlow, R.J. Schueyen, K. Wolf and K. Kardewitz, Eds.) pp. 25–37. Walter de Gruyter, New York.Google Scholar
  20. A.M. Hruszkewycz (unpublished results).Google Scholar
  21. 21.
    S. Inouye, Site-specific cleavage of double-stranded DNA by hydroperoxide of linoleic acid. FEBS Letters 172, 231–234 (1984).PubMedCrossRefGoogle Scholar
  22. 22.
    R.M. Fourney, P.J. O’Brien and W.S. Davidson, Peroxidase catalyzed aggregation of plasmid pBR322 DNA by benzidine metabolites in vitro. Carcinogenesis 7, 1535–1542 (1985).CrossRefGoogle Scholar
  23. 23.
    W.M. Brown, Mechanisms of evolution in animal mitochondrial DNA. Annals New York Acad. Sci. 361, 119–134 (1980).CrossRefGoogle Scholar
  24. 24.
    W.M. Brown, M. George Jr. and A.C. Wilson, Rapid evolution of animal mitochondrial DNA. Proc. Nat. Acad. Sci. 76, 1967–1971 (1979).PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • Andrew M. Hruszkewycz
    • 1
  1. 1.Department of PathologyGeorge Washington University Medical CenterUSA

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