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)


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).


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

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