Skip to main content
NCBI home page
Environmental Health Perspectives logoLink to Environmental Health Perspectives
. 1994 Sep;102(Suppl 3):57–61. doi: 10.1289/ehp.94102s357

Mutagenesis by metal-induced oxygen radicals.

T M Reid 1, D I Feig 1, L A Loeb 1
PMCID: PMC1567416  PMID: 7843138

Abstract

To assess the contribution of reactive oxygen species (ROS) to metal-induced mutagenesis, we have determined the spectrum of mutations in the lacZ alpha gene after exposure of M13mp2 DNA to Fe2+, Cu2+, and Ni2+. With iron and copper ions, mutations are clustered and are predominantly single-base substitutions. Fe, Cu, and phorbol ester-stimulated neutrophils also produced tandem double CC-->TT mutations. This mutation may provide a marker for the role of oxidative damage in carcinogenesis. Mutagenesis by Ni2+ required the complexing of the metal to a tripeptide and the addition of H2O2. To assess the contribution of ROS in mammalian cells, we determined the spectrum of mutations produced when purified DNA polymerases-alpha and -beta synthesized DNA using a template that had been damaged by ROS. The mutation spectra produced by the two polymerases indicates that these enzymes substitute different nucleotides opposite the same lesions.

Full text

PDF
57

Selected References

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

  1. Ames B. N. Dietary carcinogens and anticarcinogens. Oxygen radicals and degenerative diseases. Science. 1983 Sep 23;221(4617):1256–1264. doi: 10.1126/science.6351251. [DOI] [PubMed] [Google Scholar]
  2. Armstrong J. D., Kunz B. A. Site and strand specificity of UVB mutagenesis in the SUP4-o gene of yeast. Proc Natl Acad Sci U S A. 1990 Nov;87(22):9005–9009. doi: 10.1073/pnas.87.22.9005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bebenek K., Abbotts J., Roberts J. D., Wilson S. H., Kunkel T. A. Specificity and mechanism of error-prone replication by human immunodeficiency virus-1 reverse transcriptase. J Biol Chem. 1989 Oct 5;264(28):16948–16956. [PubMed] [Google Scholar]
  4. Britigan B. E., Rosen G. M., Chai Y., Cohen M. S. Do human neutrophils make hydroxyl radical? Determination of free radicals generated by human neutrophils activated with a soluble or particulate stimulus using electron paramagnetic resonance spectrometry. J Biol Chem. 1986 Apr 5;261(10):4426–4431. [PubMed] [Google Scholar]
  5. Cerutti P. A. Prooxidant states and tumor promotion. Science. 1985 Jan 25;227(4685):375–381. doi: 10.1126/science.2981433. [DOI] [PubMed] [Google Scholar]
  6. Cheng K. C., Cahill D. S., Kasai H., Nishimura S., Loeb L. A. 8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G----T and A----C substitutions. J Biol Chem. 1992 Jan 5;267(1):166–172. [PubMed] [Google Scholar]
  7. Cheng K. C., Preston B. D., Cahill D. S., Dosanjh M. K., Singer B., Loeb L. A. The vinyl chloride DNA derivative N2,3-ethenoguanine produces G----A transitions in Escherichia coli. Proc Natl Acad Sci U S A. 1991 Nov 15;88(22):9974–9978. doi: 10.1073/pnas.88.22.9974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Frenkel K., Chrzan K., Troll W., Teebor G. W., Steinberg J. J. Radiation-like modification of bases in DNA exposed to tumor promoter-activated polymorphonuclear leukocytes. Cancer Res. 1986 Nov;46(11):5533–5540. [PubMed] [Google Scholar]
  9. Fridovich I. Superoxide radical: an endogenous toxicant. Annu Rev Pharmacol Toxicol. 1983;23:239–257. doi: 10.1146/annurev.pa.23.040183.001323. [DOI] [PubMed] [Google Scholar]
  10. Halliwell B., Aruoma O. I. DNA damage by oxygen-derived species. Its mechanism and measurement in mammalian systems. FEBS Lett. 1991 Apr 9;281(1-2):9–19. doi: 10.1016/0014-5793(91)80347-6. [DOI] [PubMed] [Google Scholar]
  11. Harris C. C. Chemical and physical carcinogenesis: advances and perspectives for the 1990s. Cancer Res. 1991 Sep 15;51(18 Suppl):5023s–5044s. [PubMed] [Google Scholar]
  12. Hollstein M., Sidransky D., Vogelstein B., Harris C. C. p53 mutations in human cancers. Science. 1991 Jul 5;253(5015):49–53. doi: 10.1126/science.1905840. [DOI] [PubMed] [Google Scholar]
  13. Hutchinson F. Chemical changes induced in DNA by ionizing radiation. Prog Nucleic Acid Res Mol Biol. 1985;32:115–154. doi: 10.1016/s0079-6603(08)60347-5. [DOI] [PubMed] [Google Scholar]
  14. Jackson J. H., Gajewski E., Schraufstatter I. U., Hyslop P. A., Fuciarelli A. F., Cochrane C. G., Dizdaroglu M. Damage to the bases in DNA induced by stimulated human neutrophils. J Clin Invest. 1989 Nov;84(5):1644–1649. doi: 10.1172/JCI114342. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Joenje H. Genetic toxicology of oxygen. Mutat Res. 1989 Jul;219(4):193–208. doi: 10.1016/0921-8734(89)90001-5. [DOI] [PubMed] [Google Scholar]
  16. Kasprzak K. S. The role of oxidative damage in metal carcinogenicity. Chem Res Toxicol. 1991 Nov-Dec;4(6):604–615. doi: 10.1021/tx00024a002. [DOI] [PubMed] [Google Scholar]
  17. Klebanoff S. J. Oxygen metabolism and the toxic properties of phagocytes. Ann Intern Med. 1980 Sep;93(3):480–489. doi: 10.7326/0003-4819-93-3-480. [DOI] [PubMed] [Google Scholar]
  18. Klein C. B., Frenkel K., Costa M. The role of oxidative processes in metal carcinogenesis. Chem Res Toxicol. 1991 Nov-Dec;4(6):592–604. doi: 10.1021/tx00024a001. [DOI] [PubMed] [Google Scholar]
  19. Kunkel T. A. Mutational specificity of depurination. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1494–1498. doi: 10.1073/pnas.81.5.1494. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Kunkel T. A. The mutational specificity of DNA polymerase-beta during in vitro DNA synthesis. Production of frameshift, base substitution, and deletion mutations. J Biol Chem. 1985 May 10;260(9):5787–5796. [PubMed] [Google Scholar]
  21. Kunkel T. A. The mutational specificity of DNA polymerases-alpha and -gamma during in vitro DNA synthesis. J Biol Chem. 1985 Oct 15;260(23):12866–12874. [PubMed] [Google Scholar]
  22. Lewis J. G., Adams D. O. Induction of 5,6-ring-saturated thymine bases in NIH-3T3 cells by phorbol ester-stimulated macrophages: role of reactive oxygen intermediates. Cancer Res. 1985 Mar;45(3):1270–1275. [PubMed] [Google Scholar]
  23. McBride T. J., Preston B. D., Loeb L. A. Mutagenic spectrum resulting from DNA damage by oxygen radicals. Biochemistry. 1991 Jan 8;30(1):207–213. doi: 10.1021/bi00215a030. [DOI] [PubMed] [Google Scholar]
  24. McBride T. J., Schneider J. E., Floyd R. A., Loeb L. A. Mutations induced by methylene blue plus light in single-stranded M13mp2. Proc Natl Acad Sci U S A. 1992 Aug 1;89(15):6866–6870. doi: 10.1073/pnas.89.15.6866. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Miller J. H. Mutagenic specificity of ultraviolet light. J Mol Biol. 1985 Mar 5;182(1):45–65. doi: 10.1016/0022-2836(85)90026-9. [DOI] [PubMed] [Google Scholar]
  26. Protić-Sabljić M., Tuteja N., Munson P. J., Hauser J., Kraemer K. H., Dixon K. UV light-induced cyclobutane pyrimidine dimers are mutagenic in mammalian cells. Mol Cell Biol. 1986 Oct;6(10):3349–3356. doi: 10.1128/mcb.6.10.3349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Reid T. M., Loeb L. A. Mutagenic specificity of oxygen radicals produced by human leukemia cells. Cancer Res. 1992 Mar 1;52(5):1082–1086. [PubMed] [Google Scholar]
  28. Schaaper R. M., Dunn R. L., Glickman B. W. Mechanisms of ultraviolet-induced mutation. Mutational spectra in the Escherichia coli lacI gene for a wild-type and an excision-repair-deficient strain. J Mol Biol. 1987 Nov 20;198(2):187–202. doi: 10.1016/0022-2836(87)90305-6. [DOI] [PubMed] [Google Scholar]
  29. Stevens R. G., Jones D. Y., Micozzi M. S., Taylor P. R. Body iron stores and the risk of cancer. N Engl J Med. 1988 Oct 20;319(16):1047–1052. doi: 10.1056/NEJM198810203191603. [DOI] [PubMed] [Google Scholar]
  30. Sunderman F. W., Jr Recent advances in metal carcinogenesis. Ann Clin Lab Sci. 1984 Mar-Apr;14(2):93–122. [PubMed] [Google Scholar]
  31. Teebor G. W., Boorstein R. J., Cadet J. The repairability of oxidative free radical mediated damage to DNA: a review. Int J Radiat Biol. 1988 Aug;54(2):131–150. doi: 10.1080/09553008814551591. [DOI] [PubMed] [Google Scholar]
  32. Teoule R., Cadet J. Radiation-induced degradation of the base component in DNA and related substances--final products. Mol Biol Biochem Biophys. 1978;27:171–203. doi: 10.1007/978-3-642-81196-8_9. [DOI] [PubMed] [Google Scholar]
  33. Tkeshelashvili L. K., McBride T., Spence K., Loeb L. A. Mutation spectrum of copper-induced DNA damage. J Biol Chem. 1991 Apr 5;266(10):6401–6406. [PubMed] [Google Scholar]
  34. Wagner J. R., Hu C. C., Ames B. N. Endogenous oxidative damage of deoxycytidine in DNA. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3380–3384. doi: 10.1073/pnas.89.8.3380. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Weitzman S. A., Gordon L. I. Inflammation and cancer: role of phagocyte-generated oxidants in carcinogenesis. Blood. 1990 Aug 15;76(4):655–663. [PubMed] [Google Scholar]
  36. Wood M. L., Dizdaroglu M., Gajewski E., Essigmann J. M. Mechanistic studies of ionizing radiation and oxidative mutagenesis: genetic effects of a single 8-hydroxyguanine (7-hydro-8-oxoguanine) residue inserted at a unique site in a viral genome. Biochemistry. 1990 Jul 31;29(30):7024–7032. doi: 10.1021/bi00482a011. [DOI] [PubMed] [Google Scholar]
  37. Wood R. D., Skopek T. R., Hutchinson F. Changes in DNA base sequence induced by targeted mutagenesis of lambda phage by ultraviolet light. J Mol Biol. 1984 Mar 5;173(3):273–291. doi: 10.1016/0022-2836(84)90121-9. [DOI] [PubMed] [Google Scholar]

Articles from Environmental Health Perspectives are provided here courtesy of National Institute of Environmental Health Sciences

RESOURCES