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PMID: 2667984 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S. Review

Oxidation of DNA bases by tumor promoter-activated processes.

Environmental health perspectives ·Vol. 81 ·1989-05-00 ·Pages 45-54

Frenkel K

Abstract

Evidence has accumulated showing that active oxygen species participate in at least one stage of tumor promotion. Tumor promoters can induce various types of cells to undergo processes that result in formation of active oxygen species. They stimulate polymorphonuclear leukocytes (PMNs) to undergo an oxidative burst that is characterized by rapid formation of .O2- and H2O2. We find that in vitro formation of H2O2 by tumor promoter-activated PMNs correlates with their in vivo first-stage promoting activity. Moreover, two thymidine derivatives are formed in DNA coincubated with tumor promoter-stimulated PMNs: 5-hydroxymethyl-2'-deoxyuridine (HMdU) and thymidine glycol (dTG). The amounts of HMdU and dTG formed correlate with the first-stage tumor-promoting potencies of the agents used for PMN stimulation and with the amount of H2O2 generated. We find that HMdU is also formed in the DNA of HeLa cells coincubated with 12-O-tetradecanoylphorbol-13-acetate (TPA)-activated PMNs, with the amount of HMdU being proportional to that of TPA used. Even in the absence of PMNs, HMdU is increasingly formed in cellular DNA with increased TPA concentration, although at much lower levels than in the presence of PMNs. When rat liver microsomes are incubated with benzo[a]pyrene (BaP), a complete carcinogen, H2O2 is also generated. Production of H2O2 increases linearly with increasing concentrations of BaP. Furthermore, HMdU is formed in DNA exposed to BaP-treated microsomes, and its formation is inhibited by catalase. These results suggest that carcinogen-induced processes generating H2O2 are associated with the first-stage promoting activity of complete carcinogens.

MeSH Terms
Animals Carcinogens/pharmacology DNA/drug effects,metabolism Humans Hydrogen Peroxide/biosynthesis Neutrophils/drug effects,metabolism Oxidation-Reduction/drug effects Plasma/metabolism Thymidine/analogs & derivatives,biosynthesis
Chemicals
Carcinogens thymidine glycol 5-hydroxymethyl-2'-deoxyuridine DNA Hydrogen Peroxide Thymidine
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Frenkel K
Department of Environmental Medicine and Pathology, New York University Medical Center, NY 10016.
References (70)
70 references, click to expand
  1. Ionizing radiation and tritium transmutation both cause formation of 5-hydroxymethyl-2'-deoxyuridine in cellular DNA.
    Proc Natl Acad Sci U S A. 1984 Jan;81(2):318-21 PMID: 6582490
  2. Correlation between induction of duodenal tumor by hydrogen peroxide and catalase activity in mice.
    Gan. 1984 Jan;75(1):17-21 PMID: 6724224
  3. Iron mobilization from ferritin by superoxide derived from stimulated polymorphonuclear leukocytes. Possible mechanism in inflammation diseases.
    J Clin Invest. 1984 Jun;73(6):1576-9 PMID: 6327764
  4. Inhibition of free radical-induced DNA damage by uric acid.
    FEBS Lett. 1984 Aug 20;174(1):147-50 PMID: 6547913
  5. 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):1270-5 PMID: 3971373
  6. Retinoyl-phorbol-acetate is a complete skin tumor promoter in SENCAR mice.
    Cancer Lett. 1985 Jul;27(3):323-7 PMID: 4016727
  7. Active oxygen species and the functions of phagocytic leukocytes.
    Annu Rev Biochem. 1980;49:695-726 PMID: 6250449
  8. Studies on the mechanism of skin tumor promotion: evidence for several stages in promotion.
    Proc Natl Acad Sci U S A. 1980 Jun;77(6):3659-63 PMID: 6774342
  9. Oxygen metabolism and the toxic properties of phagocytes.
    Ann Intern Med. 1980 Sep;93(3):480-9 PMID: 6254418
  10. Stimulation of human polymorphonuclear leukocyte superoxide anion radical production by tumor promoters.
    Cancer Lett. 1981 Jan;11(3):257-62 PMID: 6265062
  11. Hydrogen peroxide causes the fatal injury to human fibroblasts exposed to oxygen radicals.
    J Biol Chem. 1981 Jul 25;256(14):7181-6 PMID: 6265440
  12. Searches for ultimate chemical carcinogens and their reactions with cellular macromolecules.
    Cancer. 1981 May 15;47(10):2327-45 PMID: 7272889
  13. Superoxide anion and hydrogen peroxide production by chemically elicited peritoneal macrophages--induction by multiple nonphagocytic stimuli.
    Cell Immunol. 1981 Apr;59(2):301-18 PMID: 6269759
  14. Identification of the cis-thymine glycol moiety in chemically oxidized and gamma-irradiated deoxyribonucleic acid by high-pressure liquid chromatography analysis.
    Biochemistry. 1981 Dec 22;20(26):7566-71 PMID: 7326245
  15. Quantitative determination of the 5-(hydroxymethyl)uracil moiety in the DNA of gamma-irradiated cells.
    Biochemistry. 1985 Aug 13;24(17):4527-33 PMID: 3904829
  16. Possible role for thymine glycol in the selective inhibition of DNA synthesis on oxidized DNA templates.
    Cancer Res. 1985 Dec;45(12 Pt 1):6113-8 PMID: 3904979
  17. Thymine glycols and urea residues in M13 DNA constitute replicative blocks in vitro.
    Nucleic Acids Res. 1985 Nov 25;13(22):8035-52 PMID: 3906566
  18. Benzo[a]pyrene dione-benzo[a]pyrene diol oxidation-reduction couples; involvement in DNA damage, cellular toxicity, and carcinogenesis.
    J Toxicol Environ Health. 1985;16(5):679-91 PMID: 3005601
  19. Enhanced malignant progression of mouse skin tumors by the free-radical generator benzoyl peroxide.
    Cancer Res. 1986 Jun;46(6):2863-5 PMID: 3084079
  20. Three-stage tumorigenesis in mouse skin: DNA synthesis as a prerequisite for the conversion stage induced by TPA prior to initiation.
    Carcinogenesis. 1986 May;7(5):779-82 PMID: 3084118
  21. Augmentation of 1,2-dimethylhydrazine-induced colon cancer by experimental colitis in mice: role of dietary vitamin E.
    J Natl Cancer Inst. 1986 May;76(5):939-42 PMID: 3457978
  22. Oxygen free radicals and iron in relation to biology and medicine: some problems and concepts.
    Arch Biochem Biophys. 1986 May 1;246(2):501-14 PMID: 3010861
  23. Role of metals in oxygen radical reactions.
    J Free Radic Biol Med. 1985;1(1):3-25 PMID: 3013969
  24. Formation of 8-hydroxydeoxyguanosine, hydroxyl free radical adduct of DNA in granulocytes exposed to the tumor promoter, tetradecanoylphorbolacetate.
    Biochem Biophys Res Commun. 1986 Jun 13;137(2):841-6 PMID: 3729941
  25. Correlation between formation of a specific hydrocarbon-deoxyribonucleoside adduct and tumor-initiating activity of 7,12-dimethylbenz(a)anthracene and its 9- and 10-monofluoroderivatives in mice.
    Cancer Res. 1986 Sep;46(9):4336-41 PMID: 3089589
  26. Neutrophil-endothelial cell interaction. Evidence for and mechanisms of the self-protection of bovine microvascular endothelial cells from hydrogen peroxide-induced oxidative stress.
    J Clin Invest. 1986 Aug;78(2):462-71 PMID: 3734101
  27. Radiation-like modification of bases in DNA exposed to tumor promoter-activated polymorphonuclear leukocytes.
    Cancer Res. 1986 Nov;46(11):5533-40 PMID: 3756901
  28. Biochemical analysis of toxic effects of 5-hydroxymethyl-2'-deoxyuridine in mammalian cells.
    Somat Cell Mol Genet. 1986 Sep;12(5):501-12 PMID: 3464103
  29. Formation of 8-hydroxyguanine residues in cellular DNA exposed to the carcinogen 4-nitroquinoline 1-oxide.
    Biochem Biophys Res Commun. 1986 Sep 14;139(2):626-32 PMID: 3094520
  30. Indirect induction of a clastogenic effect in epidermal cells by a tumor promoter.
    Carcinogenesis. 1985 Sep;6(9):1279-84 PMID: 4028325
  31. Toxicologic and antitumor studies on 5-hydroxymethyldeoxyuridine.
    Toxicol Appl Pharmacol. 1985 Jul;79(3):423-35 PMID: 4035687
  32. Wounding and its role in RSV-mediated tumor formation.
    Science. 1985 Nov 8;230(4726):676-8 PMID: 2996144
  33. Protection of mammalian cells by o-phenanthroline from lethal and DNA-damaging effects produced by active oxygen species.
    Biochim Biophys Acta. 1985 Oct 30;847(1):82-9 PMID: 2996616
  34. An examination of the DNA damaging and repair inhibitory capacity of phorbol myristate acetate in human diploid fibroblasts.
    Carcinogenesis. 1985 Nov;6(11):1667-70 PMID: 4053284
  35. 5-Hydroxymethyl-2'-deoxyuridine. Cytotoxicity and DNA incorporation studied by using a novel [2-14C]-derivative with normal and leukemic human hematopoietic cells.
    Acta Chem Scand B. 1985;39(6):477-84 PMID: 4060961
  36. Cancer in man at site of prior benign lesion of skin or mucous membrane: a review.
    Cancer Res. 1972 Jul;32(7):1359-74 PMID: 4555382
  37. Structures of benzo(a)pyrene--nucleic acid adducts formed in human and bovine bronchial explants.
    Nature. 1977 Sep 22;269(5626):348-50 PMID: 904688
  38. Thymine fragment damage retained in the DNA polynucleotide chain after gamma irradiation in aerated solutions. II.
    Radiat Res. 1977 Nov;72(2):190-200 PMID: 918256
  39. Hydrogen peroxide release from mouse peritoneal macrophages: dependence on sequential activation and triggering.
    J Exp Med. 1977 Dec 1;146(6):1648-62 PMID: 925614
  40. Benzo[alpha]pyrene diol epoxide covalently binds to deoxyguanosine and deoxyadenosine in DNA.
    Nature. 1977 Oct 20;269(5630):725-7 PMID: 304179
  41. Excisability and persistence of benzo(a)pyrene DNA adducts in epithelioid human lung cells.
    Nature. 1978 Aug 24;274(5673):796-8 PMID: 683316
  42. The biology of oxygen radicals.
    Science. 1978 Sep 8;201(4359):875-80 PMID: 210504
  43. Comparative study of oxidation of nucleic acid components by hydroxyl radicals, singlet oxygen and superoxide anion radicals.
    Photochem Photobiol. 1978 Oct-Nov;28(4-5):661-7 PMID: 216029
  44. A quantitative determination of the covalent binding of a series of polycylic hydrocarbons to DNA in mouse skin.
    Int J Cancer. 1979 Feb;23(2):201-8 PMID: 761942
  45. Myeloperoxidase, hydrogen peroxide, chloride antimicrobial system: nitrogen-chlorine derivatives of bacterial components in bactericidal action against Escherichia coli.
    Infect Immun. 1979 Feb;23(2):522-31 PMID: 217834
  46. In vivo covalent binding of organic chemicals to DNA as a quantitative indicator in the process of chemical carcinogenesis.
    Mutat Res. 1979 Dec;65(4):289-356 PMID: 390383
  47. Constitutive and induced hepatic microsomal cytochrome P-450 monooxygenase activities in male Fischer-344 and CD rats. A comparative study.
    Toxicol Appl Pharmacol. 1980 Jan;52(1):45-53 PMID: 6767296
  48. Differences in the mechanism of NADPH- and cumene hydroperoxide-supported reactions of cytochrome P-450.
    Arch Biochem Biophys. 1980 Mar;200(1):186-95 PMID: 6767447
  49. Spontaneous cancer and its possible relationship to oxygen metabolism.
    Proc Natl Acad Sci U S A. 1980 Apr;77(4):1763-7 PMID: 6929519
  50. Enhanced hydrogen peroxide release from macrophages stimulated with streptococcal preparation OK-432.
    Infect Immun. 1979 Nov;26(2):779-82 PMID: 546795
  51. Formation of 8-hydroxyguanine moiety in cellular DNA by agents producing oxygen radicals and evidence for its repair.
    Carcinogenesis. 1986 Nov;7(11):1849-51 PMID: 3769133
  52. Hydrogen peroxide formation and DNA base modification by tumor promoter-activated polymorphonuclear leukocytes.
    Carcinogenesis. 1987 Mar;8(3):455-60 PMID: 3815740
  53. Stimulation of superoxide anion formation by the non-TPA type tumor promoters palytoxin and thapsigargin in porcine and human neutrophils.
    Biochem Biophys Res Commun. 1987 Mar 13;143(2):672-7 PMID: 2882751
  54. Epidermal growth factor (EGF) and tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA) stimulate PG synthesis and thymidine incorporation in cultured porcine thyroid cells.
    Biochem Biophys Res Commun. 1987 Mar 30;143(3):880-4 PMID: 3494448
  55. Iron-mediated induction of sister-chromatid exchanges by hydrogen peroxide and superoxide anion.
    Mutat Res. 1987 May;178(1):57-63 PMID: 3033488
  56. Characterization of the hydroperoxide-reducing activity of human plasma.
    Arch Biochem Biophys. 1987 Apr;254(1):9-17 PMID: 3579308
  57. Genetic effects of 5-hydroxymethyl-2'-deoxyuridine, a product of ionizing radiation.
    Mutat Res. 1987 Jun;178(2):177-86 PMID: 2953970
  58. The relative contributions of vitamin E, urate, ascorbate and proteins to the total peroxyl radical-trapping antioxidant activity of human blood plasma.
    Biochim Biophys Acta. 1987 Jun 22;924(3):408-19 PMID: 3593759
  59. Chymotrypsin-specific protease inhibitors decrease H2O2 formation by activated human polymorphonuclear leukocytes.
    Carcinogenesis. 1987 Sep;8(9):1207-12 PMID: 3621459
  60. Production of thymine glycols in DNA by radiation and chemical carcinogens as detected by a monoclonal antibody.
    Br J Cancer Suppl. 1987 Jun;8:113-7 PMID: 3477281
  61. Quantitative measurement of the diastereoisomers of cis thymidine glycol in gamma-irradiated DNA.
    Free Radic Res Commun. 1987;2(4-6):303-9 PMID: 3504811
  62. SOME BIOLOGICAL ASPECTS OF SKIN CARCINOGENISIS.
    Prog Exp Tumor Res. 1964;4:207-50 PMID: 14150247
  63. Skin tumor promotion by phorbol esters is a two-stage process.
    Proc Natl Acad Sci U S A. 1981 Dec;78(12):7722-6 PMID: 6801661
  64. Specificity and mechanism(s) of promoter inhibitors in multistage promotion.
    Carcinog Compr Surv. 1982;7:19-34 PMID: 7039828
  65. The role of free oxygen radicals in tumor promotion and carcinogenesis.
    Carcinog Compr Surv. 1982;7:593-7 PMID: 6279300
  66. Role of oxygen-derived free radicals and metabolites in leukocyte-dependent inflammatory reactions.
    Am J Pathol. 1982 Jun;107(3):395-418 PMID: 6282132
  67. Tumor promotion by phorbol esters in skin: evidence for a memory effect.
    Science. 1983 Apr 1;220(4592):89-91 PMID: 6828884
  68. Radiation effects on DNA. The Silvanus Thompson Memorial Lecture, April 1982.
    Br J Radiol. 1983 Apr;56(664):221-31 PMID: 6831144
  69. Metabolism of polycyclic aromatic hydrocarbon derivatives to ultimate carcinogens during lipid peroxidation.
    Science. 1983 Jul 1;221(4605):77-9 PMID: 6304879
  70. Products of binding of 7,12-dimethylbenz(a)anthracene to DNA in mouse skin.
    Cancer Res. 1983 Dec;43(12 Pt 1):5647-51 PMID: 6315214
Article Info
Journal
Environmental health perspectives
Abbr.
Environ Health Perspect
ISSN
0091-6765
DOI
10.1289/ehp.898145
Published
1989-05-00
Pages
45-54
Language
English
Region
United States
NLM ID
0330411
PMCID
PMC1567529
Subset
IM
Grants
NCI NIH HHS · CA 13343 · United States
NCI NIH HHS · CA 37858 · United States
NIEHS NIH HHS · ES 00260 · United States
External Links
PubMed source DOI: 10.1289/ehp.898145 PMC Full Text View journal details
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