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. 1992 May 1;175(5):1181–1194. doi: 10.1084/jem.175.5.1181

Dithiocarbamates as potent inhibitors of nuclear factor kappa B activation in intact cells

PMCID: PMC2119220  PMID: 1314883

Abstract

Dithiocarbamates and iron chelators were recently considered for the treatment of AIDS and neurodegenerative diseases. In this study, we show that dithiocarbamates and metal chelators can potently block the activation of nuclear factor kappa B (NF-kappa B), a transcription factor involved in human immunodeficiency virus type 1 (HIV-1) expression, signaling, and immediate early gene activation during inflammatory processes. Using cell cultures, the pyrrolidine derivative of dithiocarbamate (PDTC) was investigated in detail. Micromolar amounts of PDTC reversibly suppressed the release of the inhibitory subunit I kappa B from the latent cytoplasmic form of NF-kappa B in cells treated with phorbol ester, interleukin 1, and tumor necrosis factor alpha. Other DNA binding activities and the induction of AP-1 by phorbol ester were not affected. The antioxidant PDTC also blocked the activation of NF-kappa B by bacterial lipopolysaccharide (LPS), suggesting a role of oxygen radicals in the intracellular signaling of LPS. This idea was supported by demonstrating that treatment of pre-B and B cells with LPS induced the production of O2- and H2O2. PDTC prevented specifically the kappa B-dependent transactivation of reporter genes under the control of the HIV-1 long terminal repeat and simian virus 40 enhancer. The results from this study lend further support to the idea that oxygen radicals play an important role in the activation of NF-kappa B and HIV-1.

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Selected References

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  1. Abate C., Patel L., Rauscher F. J., 3rd, Curran T. Redox regulation of fos and jun DNA-binding activity in vitro. Science. 1990 Sep 7;249(4973):1157–1161. doi: 10.1126/science.2118682. [DOI] [PubMed] [Google Scholar]
  2. Baeuerle P. A., Baltimore D. Activation of DNA-binding activity in an apparently cytoplasmic precursor of the NF-kappa B transcription factor. Cell. 1988 Apr 22;53(2):211–217. doi: 10.1016/0092-8674(88)90382-0. [DOI] [PubMed] [Google Scholar]
  3. Baeuerle P. A., Baltimore D. I kappa B: a specific inhibitor of the NF-kappa B transcription factor. Science. 1988 Oct 28;242(4878):540–546. doi: 10.1126/science.3140380. [DOI] [PubMed] [Google Scholar]
  4. Baeuerle P. A. The inducible transcription activator NF-kappa B: regulation by distinct protein subunits. Biochim Biophys Acta. 1991 Apr 16;1072(1):63–80. doi: 10.1016/0304-419x(91)90007-8. [DOI] [PubMed] [Google Scholar]
  5. Bauskin A. R., Alkalay I., Ben-Neriah Y. Redox regulation of a protein tyrosine kinase in the endoplasmic reticulum. Cell. 1991 Aug 23;66(4):685–696. doi: 10.1016/0092-8674(91)90114-e. [DOI] [PubMed] [Google Scholar]
  6. Beauchamp C., Fridovich I. Superoxide dismutase: improved assays and an assay applicable to acrylamide gels. Anal Biochem. 1971 Nov;44(1):276–287. doi: 10.1016/0003-2697(71)90370-8. [DOI] [PubMed] [Google Scholar]
  7. Bomsztyk K., Rooney J. W., Iwasaki T., Rachie N. A., Dower S. K., Sibley C. H. Evidence that interleukin-1 and phorbol esters activate NF-kappa B by different pathways: role of protein kinase C. Cell Regul. 1991 Apr;2(4):329–335. doi: 10.1091/mbc.2.4.329. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Bonser R. W., Dawson J., Thompson N. T., Hodson H. F., Garland L. G. Inhibition of phorbol ester stimulated superoxide production by 1-oleoyl-2-acetyl-sn-glycerol (OAG); fact or artefact? FEBS Lett. 1986 Dec 1;209(1):134–138. doi: 10.1016/0014-5793(86)81098-5. [DOI] [PubMed] [Google Scholar]
  9. Boyle W. J., Smeal T., Defize L. H., Angel P., Woodgett J. R., Karin M., Hunter T. Activation of protein kinase C decreases phosphorylation of c-Jun at sites that negatively regulate its DNA-binding activity. Cell. 1991 Feb 8;64(3):573–584. doi: 10.1016/0092-8674(91)90241-p. [DOI] [PubMed] [Google Scholar]
  10. Brach M. A., Hass R., Sherman M. L., Gunji H., Weichselbaum R., Kufe D. Ionizing radiation induces expression and binding activity of the nuclear factor kappa B. J Clin Invest. 1991 Aug;88(2):691–695. doi: 10.1172/JCI115354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cohen J. D., Robins H. I. Cytotoxicity of diethyldithiocarbamate in human versus rodent cell lines. Invest New Drugs. 1990 May;8(2):137–142. doi: 10.1007/BF00177247. [DOI] [PubMed] [Google Scholar]
  12. Collart M. A., Baeuerle P., Vassalli P. Regulation of tumor necrosis factor alpha transcription in macrophages: involvement of four kappa B-like motifs and of constitutive and inducible forms of NF-kappa B. Mol Cell Biol. 1990 Apr;10(4):1498–1506. doi: 10.1128/mcb.10.4.1498. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Crapper McLachlan D. R., Dalton A. J., Kruck T. P., Bell M. Y., Smith W. L., Kalow W., Andrews D. F. Intramuscular desferrioxamine in patients with Alzheimer's disease. Lancet. 1991 Jun 1;337(8753):1304–1308. doi: 10.1016/0140-6736(91)92978-b. [DOI] [PubMed] [Google Scholar]
  14. Davis N., Ghosh S., Simmons D. L., Tempst P., Liou H. C., Baltimore D., Bose H. R., Jr Rel-associated pp40: an inhibitor of the rel family of transcription factors. Science. 1991 Sep 13;253(5025):1268–1271. doi: 10.1126/science.1891714. [DOI] [PubMed] [Google Scholar]
  15. Devary Y., Gottlieb R. A., Lau L. F., Karin M. Rapid and preferential activation of the c-jun gene during the mammalian UV response. Mol Cell Biol. 1991 May;11(5):2804–2811. doi: 10.1128/mcb.11.5.2804. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Eck H. P., Gmünder H., Hartmann M., Petzoldt D., Daniel V., Dröge W. Low concentrations of acid-soluble thiol (cysteine) in the blood plasma of HIV-1-infected patients. Biol Chem Hoppe Seyler. 1989 Feb;370(2):101–108. doi: 10.1515/bchm3.1989.370.1.101. [DOI] [PubMed] [Google Scholar]
  17. Englund G., Hoggan M. D., Theodore T. S., Martin M. A. A novel HIV-1 isolate containing alterations affecting the NF-kappa B element. Virology. 1991 Mar;181(1):150–157. doi: 10.1016/0042-6822(91)90479-u. [DOI] [PubMed] [Google Scholar]
  18. Fischer S. M., Adams L. M. Suppression of tumor promoter-induced chemiluminescence in mouse epidermal cells by several inhibitors of arachidonic acid metabolism. Cancer Res. 1985 Jul;45(7):3130–3136. [PubMed] [Google Scholar]
  19. Ghosh S., Baltimore D. Activation in vitro of NF-kappa B by phosphorylation of its inhibitor I kappa B. Nature. 1990 Apr 12;344(6267):678–682. doi: 10.1038/344678a0. [DOI] [PubMed] [Google Scholar]
  20. Gorman C. M., Moffat L. F., Howard B. H. Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982 Sep;2(9):1044–1051. doi: 10.1128/mcb.2.9.1044. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Gutteridge J. M., Richmond R., Halliwell B. Inhibition of the iron-catalysed formation of hydroxyl radicals from superoxide and of lipid peroxidation by desferrioxamine. Biochem J. 1979 Nov 15;184(2):469–472. doi: 10.1042/bj1840469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Harakeh S., Jariwalla R. J., Pauling L. Suppression of human immunodeficiency virus replication by ascorbate in chronically and acutely infected cells. Proc Natl Acad Sci U S A. 1990 Sep;87(18):7245–7249. doi: 10.1073/pnas.87.18.7245. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Haskill S., Beg A. A., Tompkins S. M., Morris J. S., Yurochko A. D., Sampson-Johannes A., Mondal K., Ralph P., Baldwin A. S., Jr Characterization of an immediate-early gene induced in adherent monocytes that encodes I kappa B-like activity. Cell. 1991 Jun 28;65(7):1281–1289. doi: 10.1016/0092-8674(91)90022-q. [DOI] [PubMed] [Google Scholar]
  24. Hensel G., Männel D. N., Pfizenmaier K., Krönke M. Autocrine stimulation of TNF-alpha mRNA expression in HL-60 cells. Lymphokine Res. 1987 Spring;6(2):119–125. [PubMed] [Google Scholar]
  25. Hersh E. M., Brewton G., Abrams D., Bartlett J., Galpin J., Gill P., Gorter R., Gottlieb M., Jonikas J. J., Landesman S. Ditiocarb sodium (diethyldithiocarbamate) therapy in patients with symptomatic HIV infection and AIDS. A randomized, double-blind, placebo-controlled, multicenter study. JAMA. 1991 Mar 27;265(12):1538–1544. [PubMed] [Google Scholar]
  26. Hirschelmann R., Bekemeier H. Influence of the iron chelating agent desferrioxamine on two rat inflammatory models. Free Radic Res Commun. 1986;2(1-2):125–127. doi: 10.3109/10715768609088063. [DOI] [PubMed] [Google Scholar]
  27. Hohmann H. P., Kolbeck R., Remy R., van Loon A. P. Cyclic AMP-independent activation of transcription factor NF-kappa B in HL60 cells by tumor necrosis factors alpha and beta. Mol Cell Biol. 1991 Apr;11(4):2315–2318. doi: 10.1128/mcb.11.4.2315. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Jakway J. P., DeFranco A. L. Pertussis toxin inhibition of B cell and macrophage responses to bacterial lipopolysaccharide. Science. 1986 Nov 7;234(4777):743–746. doi: 10.1126/science.3095921. [DOI] [PubMed] [Google Scholar]
  29. Kalebic T., Kinter A., Poli G., Anderson M. E., Meister A., Fauci A. S. Suppression of human immunodeficiency virus expression in chronically infected monocytic cells by glutathione, glutathione ester, and N-acetylcysteine. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):986–990. doi: 10.1073/pnas.88.3.986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kanno M., Fromental C., Staub A., Ruffenach F., Davidson I., Chambon P. The SV40 TC-II(kappa B) and the related H-2Kb enhansons exhibit different cell type specific and inducible proto-enhancer activities, but the SV40 core sequence and the AP-2 binding site have no enhanson properties. EMBO J. 1989 Dec 20;8(13):4205–4214. doi: 10.1002/j.1460-2075.1989.tb08606.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Lang J. M., Oberling F., Aleksijevic A., Falkenrodt A., Mayer S. Immunomodulation with diethyldithiocarbamate in patients with AIDS-related complex. Lancet. 1985 Nov 9;2(8463):1066–1066. doi: 10.1016/s0140-6736(85)90931-6. [DOI] [PubMed] [Google Scholar]
  32. Lang J. M., Touraine J. L., Trepo C., Choutet P., Kirstetter M., Falkenrodt A., Herviou L., Livrozet J. M., Retornaz G., Touraine F. Randomised, double-blind, placebo-controlled trial of ditiocarb sodium ('Imuthiol') in human immunodeficiency virus infection. Lancet. 1988 Sep 24;2(8613):702–706. doi: 10.1016/s0140-6736(88)90184-5. [DOI] [PubMed] [Google Scholar]
  33. Legrand-Poels S., Vaira D., Pincemail J., van de Vorst A., Piette J. Activation of human immunodeficiency virus type 1 by oxidative stress. AIDS Res Hum Retroviruses. 1990 Dec;6(12):1389–1397. doi: 10.1089/aid.1990.6.1389. [DOI] [PubMed] [Google Scholar]
  34. Loschen G., Flohé L., Chance B. Respiratory chain linked H(2)O(2) production in pigeon heart mitochondria. FEBS Lett. 1971 Nov 1;18(2):261–264. doi: 10.1016/0014-5793(71)80459-3. [DOI] [PubMed] [Google Scholar]
  35. Lutz L. M., Glende E. A., Jr, Recknagel R. O. Protection by diethyldithiocarbamate against carbon tetrachloride lethality in rats and against carbon tetrachloride-induced lipid peroxidation in vitro. Biochem Pharmacol. 1973 Jul 15;22(14):1729–1734. doi: 10.1016/0006-2952(73)90386-9. [DOI] [PubMed] [Google Scholar]
  36. Macchi M., Bornert J. M., Davidson I., Kanno M., Rosales R., Vigneron M., Xiao J. H., Fromental C., Chambon P. The SV40 TC-II(kappa B) enhanson binds ubiquitous and cell type specifically inducible nuclear proteins from lymphoid and non-lymphoid cell lines. EMBO J. 1989 Dec 20;8(13):4215–4227. doi: 10.1002/j.1460-2075.1989.tb08607.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Mansour H., Levacher M., Gougerot-Pocidalo M. A., Rouveix B., Pocidalo J. J. Diethyldithiocarbamate provides partial protection against pulmonary and lymphoid oxygen toxicity. J Pharmacol Exp Ther. 1986 Feb;236(2):476–480. [PubMed] [Google Scholar]
  38. McCord J. M., Fridovich I. Superoxide dismutase. An enzymic function for erythrocuprein (hemocuprein). J Biol Chem. 1969 Nov 25;244(22):6049–6055. [PubMed] [Google Scholar]
  39. Meichle A., Schütze S., Hensel G., Brunsing D., Krönke M. Protein kinase C-independent activation of nuclear factor kappa B by tumor necrosis factor. J Biol Chem. 1990 May 15;265(14):8339–8343. [PubMed] [Google Scholar]
  40. Meier B., Radeke H. H., Selle S., Habermehl G. G., Resch K., Sies H. Human fibroblasts release low amounts of reactive oxygen species in response to the potent phagocyte stimulants, serum-treated zymosan, N-formyl-methionyl-leucyl-phenylalanine, leukotriene B4 or 12-O-tetradecanoylphorbol 13-acetate. Biol Chem Hoppe Seyler. 1990 Oct;371(10):1021–1025. doi: 10.1515/bchm3.1990.371.2.1021. [DOI] [PubMed] [Google Scholar]
  41. Meier B., Radeke H. H., Selle S., Younes M., Sies H., Resch K., Habermehl G. G. Human fibroblasts release reactive oxygen species in response to interleukin-1 or tumour necrosis factor-alpha. Biochem J. 1989 Oct 15;263(2):539–545. doi: 10.1042/bj2630539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Mihm S., Ennen J., Pessara U., Kurth R., Dröge W. Inhibition of HIV-1 replication and NF-kappa B activity by cysteine and cysteine derivatives. AIDS. 1991 May;5(5):497–503. doi: 10.1097/00002030-199105000-00004. [DOI] [PubMed] [Google Scholar]
  43. Miyamoto M., Fujita T., Kimura Y., Maruyama M., Harada H., Sudo Y., Miyata T., Taniguchi T. Regulated expression of a gene encoding a nuclear factor, IRF-1, that specifically binds to IFN-beta gene regulatory elements. Cell. 1988 Sep 9;54(6):903–913. doi: 10.1016/s0092-8674(88)91307-4. [DOI] [PubMed] [Google Scholar]
  44. Nabel G., Baltimore D. An inducible transcription factor activates expression of human immunodeficiency virus in T cells. Nature. 1987 Apr 16;326(6114):711–713. doi: 10.1038/326711a0. [DOI] [PubMed] [Google Scholar]
  45. Negre-Salvayre A., Reaud V., Hariton C., Salvayre R. Protective effect of alpha-tocopherol, ascorbic acid and rutin against peroxidative stress induced by oxidized lipoproteins on lymphoid cell lines. Biochem Pharmacol. 1991 Jul 5;42(2):450–453. doi: 10.1016/0006-2952(91)90737-p. [DOI] [PubMed] [Google Scholar]
  46. Nose K., Shibanuma M., Kikuchi K., Kageyama H., Sakiyama S., Kuroki T. Transcriptional activation of early-response genes by hydrogen peroxide in a mouse osteoblastic cell line. Eur J Biochem. 1991 Oct 1;201(1):99–106. doi: 10.1111/j.1432-1033.1991.tb16261.x. [DOI] [PubMed] [Google Scholar]
  47. Osborn L., Kunkel S., Nabel G. J. Tumor necrosis factor alpha and interleukin 1 stimulate the human immunodeficiency virus enhancer by activation of the nuclear factor kappa B. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2336–2340. doi: 10.1073/pnas.86.7.2336. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Perchellet E. M., Maatta E. A., Abney N. L., Perchellet J. P. Effects of diverse intracellular thiol delivery agents on glutathione peroxidase activity, the ratio of reduced/oxidized glutathione, and ornithine decarboxylase induction in isolated mouse epidermal cells treated with 12-O-tetradecanoylphorbol-13-acetate. J Cell Physiol. 1987 Apr;131(1):64–73. doi: 10.1002/jcp.1041310111. [DOI] [PubMed] [Google Scholar]
  49. Phares W., Herr W. Functional similarities between human immunodeficiency virus type 1 and simian virus 40 kappa B proto-enhancers. J Virol. 1991 May;65(5):2200–2210. doi: 10.1128/jvi.65.5.2200-2210.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Polonis V. R., Anderson G. R., Vahey M. T., Morrow P. J., Stoler D., Redfield R. R. Anoxia induces human immunodeficiency virus expression in infected T cell lines. J Biol Chem. 1991 Jun 25;266(18):11421–11424. [PubMed] [Google Scholar]
  51. Pomerantz R. J., Feinberg M. B., Trono D., Baltimore D. Lipopolysaccharide is a potent monocyte/macrophage-specific stimulator of human immunodeficiency virus type 1 expression. J Exp Med. 1990 Jul 1;172(1):253–261. doi: 10.1084/jem.172.1.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Reisinger E. C., Kern P., Ernst M., Bock P., Flad H. D., Dietrich M. Inhibition of HIV progression by dithiocarb. German DTC Study Group. Lancet. 1990 Mar 24;335(8691):679–682. doi: 10.1016/0140-6736(90)90802-c. [DOI] [PubMed] [Google Scholar]
  53. Roederer M., Staal F. J., Raju P. A., Ela S. W., Herzenberg L. A., Herzenberg L. A. Cytokine-stimulated human immunodeficiency virus replication is inhibited by N-acetyl-L-cysteine. Proc Natl Acad Sci U S A. 1990 Jun;87(12):4884–4888. doi: 10.1073/pnas.87.12.4884. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Rosenberg Z. F., Fauci A. S. Immunopathogenic mechanisms of HIV infection: cytokine induction of HIV expression. Immunol Today. 1990 May;11(5):176–180. doi: 10.1016/0167-5699(90)90070-p. [DOI] [PubMed] [Google Scholar]
  55. Rosoff P. M., Savage N., Dinarello C. A. Interleukin-1 stimulates diacylglycerol production in T lymphocytes by a novel mechanism. Cell. 1988 Jul 1;54(1):73–81. doi: 10.1016/0092-8674(88)90181-x. [DOI] [PubMed] [Google Scholar]
  56. Sando J. J., Hilfiker M. L., Salomon D. S., Farrar J. J. Specific receptors for phorbol esters in lymphoid cell populations: role in enhanced production of T-cell growth factor. Proc Natl Acad Sci U S A. 1981 Feb;78(2):1189–1193. doi: 10.1073/pnas.78.2.1189. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Schreck R., Baeuerle P. A. A role for oxygen radicals as second messengers. Trends Cell Biol. 1991 Aug;1(2-3):39–42. doi: 10.1016/0962-8924(91)90072-h. [DOI] [PubMed] [Google Scholar]
  58. Schreck R., Baeuerle P. A. NF-kappa B as inducible transcriptional activator of the granulocyte-macrophage colony-stimulating factor gene. Mol Cell Biol. 1990 Mar;10(3):1281–1286. doi: 10.1128/mcb.10.3.1281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Schreck R., Rieber P., Baeuerle P. A. Reactive oxygen intermediates as apparently widely used messengers in the activation of the NF-kappa B transcription factor and HIV-1. EMBO J. 1991 Aug;10(8):2247–2258. doi: 10.1002/j.1460-2075.1991.tb07761.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Sen R., Baltimore D. Inducibility of kappa immunoglobulin enhancer-binding protein Nf-kappa B by a posttranslational mechanism. Cell. 1986 Dec 26;47(6):921–928. doi: 10.1016/0092-8674(86)90807-x. [DOI] [PubMed] [Google Scholar]
  61. Sen R., Baltimore D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell. 1986 Aug 29;46(5):705–716. doi: 10.1016/0092-8674(86)90346-6. [DOI] [PubMed] [Google Scholar]
  62. Staal F. J., Roederer M., Herzenberg L. A., Herzenberg L. A. Intracellular thiols regulate activation of nuclear factor kappa B and transcription of human immunodeficiency virus. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9943–9947. doi: 10.1073/pnas.87.24.9943. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Steiner C., Muller M., Baniahmad A., Renkawitz R. Lysozyme gene activity in chicken macrophages is controlled by positive and negative regulatory elements. Nucleic Acids Res. 1987 May 26;15(10):4163–4178. doi: 10.1093/nar/15.10.4163. [DOI] [PMC free article] [PubMed] [Google Scholar]
  64. Storz G., Tartaglia L. A., Ames B. N. Transcriptional regulator of oxidative stress-inducible genes: direct activation by oxidation. Science. 1990 Apr 13;248(4952):189–194. doi: 10.1126/science.2183352. [DOI] [PubMed] [Google Scholar]
  65. Urban M. B., Schreck R., Baeuerle P. A. NF-kappa B contacts DNA by a heterodimer of the p50 and p65 subunit. EMBO J. 1991 Jul;10(7):1817–1825. doi: 10.1002/j.1460-2075.1991.tb07707.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Wightman P. D., Raetz C. R. The activation of protein kinase C by biologically active lipid moieties of lipopolysaccharide. J Biol Chem. 1984 Aug 25;259(16):10048–10052. [PubMed] [Google Scholar]
  67. Wong G. H., Elwell J. H., Oberley L. W., Goeddel D. V. Manganous superoxide dismutase is essential for cellular resistance to cytotoxicity of tumor necrosis factor. Cell. 1989 Sep 8;58(5):923–931. doi: 10.1016/0092-8674(89)90944-6. [DOI] [PubMed] [Google Scholar]
  68. Wong G. H., Goeddel D. V. Induction of manganous superoxide dismutase by tumor necrosis factor: possible protective mechanism. Science. 1988 Nov 11;242(4880):941–944. doi: 10.1126/science.3263703. [DOI] [PubMed] [Google Scholar]
  69. Zabel U., Schreck R., Baeuerle P. A. DNA binding of purified transcription factor NF-kappa B. Affinity, specificity, Zn2+ dependence, and differential half-site recognition. J Biol Chem. 1991 Jan 5;266(1):252–260. [PubMed] [Google Scholar]
  70. de Mello Filho A. C., Meneghini R. 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):82–89. doi: 10.1016/0167-4889(85)90156-9. [DOI] [PubMed] [Google Scholar]

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