Skip to main content
Biochemical Journal logoLink to Biochemical Journal
. 1982 Aug 1;205(2):321–329. doi: 10.1042/bj2050321

Iron-induced DNA damage and synthesis in isolated rat liver nuclei.

T K Shires
PMCID: PMC1158484  PMID: 7138506

Abstract

Incubation of iron with isolated rat liver nuclei stimulated fragmentation of single-stranded DNA, incorporation of [3H]thymidine into DNA and the binding of 59Fe to DNA. FeCl2 was about twice as active as FeCl3. Lipid peroxidation took place in nuclei incubated with FeCl2, but not with FeCl3. Generation of reactive forms of oxygen was required for iron-mediated DNA damage, but evidence for direct interaction of reactive oxygen with DNA was not found. Apparent adducts of iron bound to DNA seemed to be formed by an enzymic mechanism.

Full text

PDF
321

Selected References

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

  1. BURTON K. A study of the conditions and mechanism of the diphenylamine reaction for the colorimetric estimation of deoxyribonucleic acid. Biochem J. 1956 Feb;62(2):315–323. doi: 10.1042/bj0620315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Baird M. B., Birnbaum L. S., Sfeir G. T. NADPH-driven lipid peroxidation in rat liver nuclei and nuclear membranes. Arch Biochem Biophys. 1980 Mar;200(1):108–115. doi: 10.1016/0003-9861(80)90337-9. [DOI] [PubMed] [Google Scholar]
  3. Benedetti A., Casini A. F., Ferrali M., Comporti M. Effects of diffusible products of peroxidation of rat liver microsomal lipids. Biochem J. 1979 May 15;180(2):303–312. doi: 10.1042/bj1800303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brooks B. R., Klamerth O. L. Interaction of DNA with bifunctional aldehydes. Eur J Biochem. 1968 Jul;5(2):178–182. doi: 10.1111/j.1432-1033.1968.tb00355.x. [DOI] [PubMed] [Google Scholar]
  5. Burger R. M., Peisach J., Blumberg W. E., Horwitz S. B. Iron-bleomycin interactions with oxygen and oxygen analogues. Effects on spectra and drug activity. J Biol Chem. 1979 Nov 10;254(21):10906–10912. [PubMed] [Google Scholar]
  6. Burgoyne L. A., Hewish D. R., Mobbs J. Mammalian chromatin substructure studies with the calcium-magnesium endonuclease and two-dimensional polyacrylamide-gel electrophoresis. Biochem J. 1974 Oct;143(1):67–72. doi: 10.1042/bj1430067. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. D'Andrea A. D., Haseltine W. A. Sequence specific cleavage of DNA by the antitumor antibiotics neocarzinostatin and bleomycin. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3608–3612. doi: 10.1073/pnas.75.8.3608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Floyd R. A. DNA-ferrous iron catalyzed hydroxyl free radical formation from hydrogen peroxide. Biochem Biophys Res Commun. 1981 Apr 30;99(4):1209–1215. doi: 10.1016/0006-291x(81)90748-8. [DOI] [PubMed] [Google Scholar]
  9. Fornace A. J., Jr, Kohn K. W., Kann H. E., Jr DNA single-strand breaks during repair of UV damage in human fibroblasts and abnormalities of repair in xeroderma pigmentosum. Proc Natl Acad Sci U S A. 1976 Jan;73(1):39–43. doi: 10.1073/pnas.73.1.39. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Halliwell B. Superoxide-dependent formation of hydroxyl radicals in the presence of iron chelates: is it a mechanism for hydroxyl radical production in biochemical systems? FEBS Lett. 1978 Aug 15;92(2):321–326. doi: 10.1016/0014-5793(78)80779-0. [DOI] [PubMed] [Google Scholar]
  11. Kirby K. S., Cook E. A. Isolation of deoxyribonucleic acid from mammalian tissues. Biochem J. 1967 Jul;104(1):254–257. doi: 10.1042/bj1040254. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kohn K. W., Erickson L. C., Ewig R. A., Friedman C. A. Fractionation of DNA from mammalian cells by alkaline elution. Biochemistry. 1976 Oct 19;15(21):4629–4637. doi: 10.1021/bi00666a013. [DOI] [PubMed] [Google Scholar]
  13. Kornbrust D. J., Mavis R. D. Microsomal lipid peroxidation. I. Characterization of the role of iron and NADPH. Mol Pharmacol. 1980 May;17(3):400–407. [PubMed] [Google Scholar]
  14. Lesko S. A., Lorentzen R. J., Ts'o P. O. Role of superoxide in deoxyribonucleic acid strand scission. Biochemistry. 1980 Jun 24;19(13):3023–3028. doi: 10.1021/bi00554a029. [DOI] [PubMed] [Google Scholar]
  15. Massie H. R., Samis H. V., Baird M. B. The kinetics of degradation of DNA and RNA by H 2 O 2 . Biochim Biophys Acta. 1972 Jul 31;272(4):539–548. doi: 10.1016/0005-2787(72)90509-6. [DOI] [PubMed] [Google Scholar]
  16. May H. E., McCay P. B. Reduced triphosphopyridine nucleotide oxidase-catalyzed alterations of membrane phospholipids. II. Enzymic properties and stoichiometry. J Biol Chem. 1968 May 10;243(9):2296–2305. [PubMed] [Google Scholar]
  17. Mukai F. H., Goldstein B. D. Mutagenicity of malonaldehyde, a decomposition product of peroxidized polyunsaturated fatty acids. Science. 1976 Feb 27;191(4229):868–869. doi: 10.1126/science.766187. [DOI] [PubMed] [Google Scholar]
  18. Pfeifer P. M., McCay P. B. Reduced triphosphopyridine nucleotide oxidase-catalyzed alterations of membrane phospholipids. VI. Structural changes in mitochondria associated with inactivation of electron transport activity. J Biol Chem. 1972 Nov 10;247(21):6763–6769. [PubMed] [Google Scholar]
  19. Povirk L. F. Catalytic release of deoxyribonucleic acid bases by oxidation and reduction of an iron.bleomycin complex. Biochemistry. 1979 Sep 4;18(18):3989–3995. doi: 10.1021/bi00585a023. [DOI] [PubMed] [Google Scholar]
  20. Poyer J. L., McCay P. B. Reduced triphosphopyridine nucleotide oxidase-catalyzed alterations of membrane phospholipids. IV. Dependence on Fe3+. J Biol Chem. 1971 Jan 10;246(1):263–269. [PubMed] [Google Scholar]
  21. Sausville E. A., Peisach J., Horwitz S. B. Effect of chelating agents and metal ions on the degradation of DNA by bleomycin. Biochemistry. 1978 Jul 11;17(14):2740–2746. doi: 10.1021/bi00607a007. [DOI] [PubMed] [Google Scholar]
  22. Shamberger R. J., Corlett C. L., Beaman K. D., Kasten B. L. Antioxidants reduce the mutagenic effect of malonaldehyde and beta-propiolactone. Part IX. Antioxidants and cancer. Mutat Res. 1979 Apr;66(4):349–355. doi: 10.1016/0165-1218(79)90045-4. [DOI] [PubMed] [Google Scholar]
  23. Shaw J. L., Blanco J., Mueller G. C. Simple procedure for isolation of DNA, RNA and protein fractions from cultured animal cells. Anal Biochem. 1975 May 12;65(1-2):125–131. doi: 10.1016/0003-2697(75)90498-4. [DOI] [PubMed] [Google Scholar]
  24. Shires T. K. Inhibition by lipoperoxidation of amino acid incorporation by rough microsomal membranes in vitro and its partial reversibility. Arch Biochem Biophys. 1975 Dec;171(2):695–7O7. doi: 10.1016/0003-9861(75)90082-x. [DOI] [PubMed] [Google Scholar]
  25. Svingen B. A., Buege J. A., O'Neal F. O., Aust S. D. The mechanism of NADPH-dependent lipid peroxidation. The propagation of lipid peroxidation. J Biol Chem. 1979 Jul 10;254(13):5892–5899. [PubMed] [Google Scholar]
  26. Takeshita M., Grollman A. P., Ohtsubo E., Ohtsubo H. Interaction of bleomycin with DNA. Proc Natl Acad Sci U S A. 1978 Dec;75(12):5983–5987. doi: 10.1073/pnas.75.12.5983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Whittle E. D., Bushnell D. E., Potter V. R. RNA associated with the outer membrane of rat liver nuclei. Biochim Biophys Acta. 1968 Jun 18;161(1):41–50. doi: 10.1016/0005-2787(68)90292-x. [DOI] [PubMed] [Google Scholar]
  28. Wills E. D. Lipid peroxide formation in microsomes. The role of non-haem iron. Biochem J. 1969 Jun;113(2):325–332. doi: 10.1042/bj1130325. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES