Advertisement

Activation of Xenobiotics by Human Polymorphonuclear Leukocytes via Reactive Oxygen-Dependent Reactions

  • Michael A. Trush
  • Thomas W. Kensler
  • John L. Seed
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 197)

Abstract

Reactive oxygen intermediates have become widely implicated in various pathologic states, chemical-induced tissue injury and chemical carcinogenesis (1–5). While much of the interest in the role of oxy-radicals in these processes has centered on the direct interaction of reactive oxygen metabolites with biomolecules, it is becoming increasingly apparent that molecular oxygen-derived oxidants can also participate in the metabolic activation of chemicals (6,7). It has been hypothesized that polymorphonuclear leukocytes (PMNs) may be a useful cellular model to study the interaction and possible activation of compounds by reactive oxygen species (Figure 1)(8,9). Resting PMNs release measurable quantities of superoxide \({{O}_{2}}\overline{.}\) ), hydrogen peroxide (H2O2) and hydroxyl radical (•OH), while activation of their redox metabolism by both particulate and soluble stimulants results in an increased rate in the generation of these molecular oxygen-derived oxidants (10,11). The utilization of H2O2 by the PMN enzyme myeloperoxidase (MPO) results in the formation of hypochlorous acid and an O2 metabolite or complex with singlet oxygen (1O2)-like reactivity (11). The data presented in this study demonstrate that bleomycin A2 and benzo[a]pyrene-7,8-dihydrodiol (BP-7,8-dihydrodiol) are activated to genotoxic derivatives as a result of their interaction with PMN-derived oxidants. Such an activation mechanism could provide an explanation as to how neoplasms often develop at sites of ongoing inflammation (12).

Keywords

Polycyclic Aromatic Hydrocarbon Covalent Binding Reactive Oxygen Metabolite Human Polymorphonuclear Leukocyte Methyl Furan 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    B.N. Ames, Dietary carcinogens and anticarcinogens: oxygen radicals and degenerative diseases, Science, 221: 1256 (1983).PubMedCrossRefGoogle Scholar
  2. 2.
    M.A. Trush, E.G. Mimnaugh and T.E. Gram, Activation of pharmacologic agents to radical intermediates: implications for the role of free radicals in drug action and toxicity, Biochem. Pharmacol., 31: 3335 (1982).Google Scholar
  3. 3.
    B. Freeman and J. Crapo, Free radicals and tissue injury, Lab. Invest., 47: 412 (1982).Google Scholar
  4. 4.
    T.W. Kensler and M.A. Trush, Role of oxygen radicals in tumor promotion, Env. Mutagenesis, 6: 593 (1984).CrossRefGoogle Scholar
  5. 5.
    T.W. Kensler and M.A. Trush, Oxygen free radicals in chemical carcinogenesis, in: “Superoxide Dismutase, Vol. III: Pathological States”, L.W. Oberley, ed., CRC Press, Boca Raton, FL, in press (1985).Google Scholar
  6. 6.
    I. Johansson and M. Ingleman Sundberg, Hydroxyl radical-mediated cytochrome P-450-dependent metabolic activation of benzene in microsomes and reconstituted enzyme systems from rabbit liver, J. Biol. Chem., 258: 7311 (1983).PubMedGoogle Scholar
  7. 7.
    E. Dybing, S.D. Nelson, J.R. Mitchell, H.A. Sasame and J.R. Gillette, Oxidation of a-methyldopa and other catechols by cytochrome P-450-generated superoxide anion: possible mechanism of methyldopa hepatitis, Mol. Pharmacol., 12: 911 (1976).Google Scholar
  8. 8.
    M.A. Trush, M.E. Wilson and K. VanDyke, The generation of chemiluminescence by phagocytic cells, in: “Methods Enzymol”, 57, M. DeLuca, ed., Academic Press, NY (1978).Google Scholar
  9. 9.
    A.A. Roman-Franco, Non-enzymatic extramicrosomal bioactivation of chemical carcinogens by phagocytes: A proposed new pathway, J. Theor. Biol., 97: 543 (1982).PubMedCrossRefGoogle Scholar
  10. 10.
    S.J. Klebanoff, Oxygen metabolism and the toxic properties of phagocytes, Ann. Inter. Med., 93: 480 (1980).Google Scholar
  11. 11.
    R.C. Allen, Biochemiexcitation: chemiluminescence and the study of biological oxygenation reactions, in: “Chemical and Biological Generation of Excited States”, W. Adam and G. Cilento, eds., Academic Press, NY, (1982).Google Scholar
  12. 12.
    H.B. Demopoulos, D.D. Pietronigro and M.L. Seligman, The development of secondary pathology with free radical reactions as a threshold mechanism, J. Amer. Coll. Toxicol., 2: 173 (1983).CrossRefGoogle Scholar
  13. 13.
    M.T. Kuo and C.W. Haidle, Characterization of chain breakage of DNA induced by bleomycin, Biochim. Biophys. Acta, 335: 109 (1973).Google Scholar
  14. 14.
    H. Umezawa, Bleomycin: discovery, chemistry and action, Gann Monogr. Cancer Res., 19: 3 (1976).Google Scholar
  15. 15.
    R.M. Burger, J. Peisach and S.B. Horwitz, Activated bleomycin - a transient complex of drug, iron and oxygen that degrades DNA, J. Biol. Chem., 256: 11636 (1981).PubMedGoogle Scholar
  16. 16.
    E.A. Sausville, J. Peisach and S.B. Horwitz, Effect of chelating agents and metal ions on the degradation of DNA by bleomycin, Biochem., 17: 2740 (1978).CrossRefGoogle Scholar
  17. 17.
    M.A. Trush and E.G. Mimnaugh, Different roles for superoxide anion in the toxic actions of bleomycin and paraquat, in: “Oxy Radicals and Their Scavenger Systems: Cellular and Medical Aspects, Vol. 2”, R. Greenwald and G. Cohen, eds., Elsevier/North Holland, New York (1983).Google Scholar
  18. 18.
    H.W. Birnboim, DNA strand breaks in human leukocytes exposed to a tumor promoter, phorbol myristate acetate, Science, 215: 1247 (1982).PubMedCrossRefGoogle Scholar
  19. 19.
    A.B. Weitberg, S.A. Weitzman, M.Destrempes, S.A. Latt and T.R. Stossel, Stimulated human phagocytes produce cytogenic changes in cultured mammalian cells, New Eng. J. Med., 308: 26 (1983).CrossRefGoogle Scholar
  20. 20.
    J.W. Lown and S-K. Sim, The mechanism of the bleomycin-induced cleavage of DNA, Biochem. Biophys. Res. Commun., 77: 1150 (1977).CrossRefGoogle Scholar
  21. 21.
    R. Ishida and T. Takahashi, Increased DNA chain breakage by combined action of bleomycin and superoxide radical, Biochem. Biophys. Res. Commun., 66: 1432 (1975).CrossRefGoogle Scholar
  22. 22.
    M.A. Trush, E.G. Mimnaugh, E. Ginsburg and T.E. Gram, Studies on the interaction of bleomycin A2 with rat lung microsomes. II. Involvement of adventitious iron and reactive oxygen in bleomycin-mediated DNA chain breakage, J. Pharmacol. Exp. Therap., 221: 159 (1982).Google Scholar
  23. 23.
    M.E. Scheulen, H. Kappus, D. Thyssen and C.G. Schmidt, Reduction cycling of Fe(III)-bleomycin by NADPH-cytochrome P-450-reductase, Biochem. Pharmacol., 30: 3385 (1981).Google Scholar
  24. 24.
    H.H. Seliger, A. Thompson, J.P. Hamman and G.H. Posner, Chemiluminescence of benzo[a]pyrene-7,8-diol, Photochem. Photobiol., 36: 359 (1982).CrossRefGoogle Scholar
  25. 25.
    T.A. Dix and L.J. Marnett, Metabolism of polyclic aromatic hydrocarbon derivatives to ultimate carcinogens during lipid peroxidation, Science, 221: 77 (1983).PubMedCrossRefGoogle Scholar
  26. 26.
    G.A. Reed, E.A. Brooks and T.E. Eling, Phenylbutazone-dependent epoxidation of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene, J. Biol. Chem. 259: 5591 (1984).PubMedGoogle Scholar
  27. 27.
    T.W. Kensler, D.M. Bush and W.J. Kozumbo, Inhibition of tumor promotion by a biomimetic superoxide dismutase, Science, 221: 75 (1983).PubMedCrossRefGoogle Scholar
  28. 28.
    T.W. Kensler and M.A. Trush, Inhibition of oxygen radical metabolism in phorbol ester-activated polymorphonuclear leukocytes by an antitumor promoting copper complex with superoxide dismutase-mimetic activity, Biochem. Pharmacol., 32: 3485 (1983).Google Scholar
  29. 29.
    W.J. Kozumbo, M.A. Trush and T.W. Kensler, Are free radicals involved in tumor promotion? Chem.-Biol. Interactions, in press (1985).Google Scholar
  30. 30.
    M.A. Trush, J.L. Seed and T.W. Kensler, Oxidant-dependent metabolic activation of polycyclic aromatic hydrocarbons by phorbol ester-stimulated human polymorphonuclear leukocytes: possible link between inflammation and cancer, Proc. Natl. Acad. Sci. USA, in press (1985).Google Scholar
  31. 31.
    M.R. Boyd, Biochemical mechanisms in chemical induced lung injury: roles of metabolic activation, CRC Crit. Rev. Toxicol., 7: 163 (1980).CrossRefGoogle Scholar
  32. 32.
    K. Takanaka, P.J. O’Brien, Y. Tsuruta and A.H. Rahimtula, Tumor promoter stimulated irreversible binding of N-methylaminobenzene to polymorphonuclear leukocytes, Cancer Letters, 15: 311 (1982).PubMedCrossRefGoogle Scholar
  33. 33.
    Y Tsuruta, V.V. Subrahmanyam, W. Marshall and P.J. O’Brien, Peroxidasemediated irreversible binding of arylamine carcinogens to DNA in intact polymorphonuclear leukocytes activated by a tumor promoter, Chem.-Biol. Interactions, 53: 25 (1985).Google Scholar
  34. 34.
    S.J. Klebanoff, Estrogen binding by leukocytes during phagocytosis, J. Exp. Med., 145: 983 (1977).PubMedCrossRefGoogle Scholar
  35. 35.
    T.W. Kensler and M.A. Trush, Inhibition of phorbol ester-stimulated chemiluminescence in human polymorphonuclear leukocytes by retinoic acid and 5,6-epoxyretinoic acid, Cancer Res., 41: 216 (1981).PubMedGoogle Scholar
  36. 36.
    M.A. Trush, M.J. Reasor, M.E. Wilson and K. VanDyke, Oxidant-mediated electronic excitation of imipramine, Biochem. Pharmacol., 33: 1401 (1984).Google Scholar
  37. 37.
    M.A. Trush, E.G. Mimnaugh, Z.H. Siddik and T.E. Gram, Bleomycin-metal interaction: ferrous iron-initiated chemiluminescence, Biochem. Biophys. Res. Commun., 112: 378 (1983).CrossRefGoogle Scholar
  38. 38.
    W.E. Antholine, T. Sarna, R.C. Sealy, B Kalyanaraman, G.D. Shields and D.H. Petering, Free radicals from the photodecomposition of bleomycin, Photochem. Photobiol., 41: 393 (1985).CrossRefGoogle Scholar
  39. 39.
    C. Borek and W. Troll, Modifiers of free radicals inhibit in vitro the oncogenic actions of x-rays, bleomycin and the tumor promoter 12–0tetradecanoyl phorbol-l3-acetate, Proc. Natl. Acad. Sci. USA, 80: 1304 (1983).PubMedCrossRefGoogle Scholar
  40. 40.
    C. Auclair, H. Gautero and P. Boivin, Effects of salicylate-copper complex on the metabolic activation in phagocytizing granulocytes, Biochem. Pharmacol., 29: 3105 (1980).Google Scholar
  41. 41.
    A.H. Conney, Induction of microsomal enzymes by foreign chemicals and carcinogenesis by polycyclic aromatic hydrocarbons: G.H.A. Clowes Memorial Lecture, Cancer Res., 42: 4875 (1982).PubMedGoogle Scholar
  42. 42.
    L.J. Marnett, Polycyclic aromatic hydrocarbon oxidation during prostaglandin biosynthesis, Life Sci., 29: 531 (1981).PubMedCrossRefGoogle Scholar
  43. 43.
    J.R. Battista, T.A. Dix and L.J. Marnett, The mechanism of hydroperoxide-dependent epoxidation of 7,8-dihydroxy-7,8-dihydrobenzo[a]pyrene by rat liver microsomes, Proc. Amer. Assoc.Cancer Res., 25: 114 (1984).Google Scholar
  44. 44.
    J. Guthrie, I.G.C. Robertson, E. Zeiger, J.A. Boyd and T.E. Eling, Selective activation of some dihydrodiols of several polycyclic aromatic hydrocarbons to mutagenic products by prostaglandin synthetase, Cancer Res., 42: 1620 (1982).PubMedGoogle Scholar
  45. 45.
    L.J. Marnett, G.A. Reed and J.T. Johnson, Prostaglandin synthetase dependent benzo[a]pyrene oxidation: products of the oxidation and inhibition of their formation by antioxidants, Biochem.Biophys. Res. Commun., 79: 569 (1977).Google Scholar
  46. 46.
    P.L. Chesis, D.E. Levin, M.T. Smith, L. Ernster and B.N. Ames, Mutageni-city of quinones: pathways of metabolic activation and detoxification, Proc. Natl. Acad. Sci. USA, 81: 1696 (1984).PubMedCrossRefGoogle Scholar
  47. 47.
    A. Faljoni, M. Haun, M.E. Hoffman, R. Meneghini, N. Duran and G. Cilento, Photochemical-like effects in DNA caused by enzymically energized triplet carbonyl compounds, Biochem. Biophys. Res. Commun., 80: 490 (1978).CrossRefGoogle Scholar
  48. 48.
    S.A. Toledo, A. Zaha and N. Duran, DNA strand scission in E. coli by electronically excited state molecules generated by enzymatic systems, Biochem. Biophys. Res. Commun., 104: 990 (1982).Google Scholar
  49. 49.
    V. Ravindranath, L.T. Burka and M.R. Boyd, Reactive metabolites from the bioactivation of toxic methylfurans, Science, 224: 884 (1984).PubMedCrossRefGoogle Scholar
  50. 50.
    H. Rosen and S.J. Kiebanoff, Formation of singlet oxygen by the myeloperoxidase-mediated antimicrobial system, J. Biol. Chem., 252: 4803 (1977).PubMedGoogle Scholar
  51. 51.
    H.C. Pitot, Biological and enzymatic _events in chemical carcinogenesis, Ann. Rev. Med., 30: 25 (1979).PubMedCrossRefGoogle Scholar
  52. 52.
    H. Hennings, R. Shores, M.L. Wenk, E.F. Spangler, R. Tarone and S.H. Yuspa, Malignant conversion of mouse skin is increased by tumor initiators and unaffected by tumor promoters, Nature, 289: 353 (1981).CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • Michael A. Trush
    • 1
  • Thomas W. Kensler
    • 1
  • John L. Seed
    • 2
  1. 1.Department of Environmental Health SciencesThe Johns Hopkins University, School of Hygiene and Public HealthBaltimoreUSA
  2. 2.lmmunology and Infectious DiseasesThe Johns Hopkins University, School of Hygiene and Public HealthBaltimoreUSA

Personalised recommendations