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Studies on Biochemical Determinants of Quinone-Induced Toxicity in Primary Murine Bone Marrow Stromal Cells

  • Lorraine E. Twerdok
  • Michael A. Trush
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 283)

Abstract

Bone marrow is a target organ for toxicities induced by a spectrum of chemicals including the environmental pollutants benzene (Snyder et al., 1981) and benzo,[a]pyrene (BP) (Nebert and Jensen, 1979). Metabolism appears to be important for the expression of hematotoxicity by these two compounds, and metabolism of BP or benzene results in a number of metabolites including redox-active quinones. It has been demonstrated that metabolites of benzene, including hydroquinone (HQ) and benzoquinone (BZQ), concentrate in the marrow, and are believed to be the proximate or active metabolites responsible for the toxic effects of benzene. In support of this, Gaido and Wierda (1984, 1985) have identified bone marrow stromal cells as targets of toxicity of several benzene metabolites, particularly hydroquinone. We hypothesize that biochemical activities, such as quinone reductase (QR; NADPH:DT diaphorase) at the level of the bone marrow may contribute to target organ specificity in chemically-induced bone marrow toxicity. Quinone reductase is a widely distributed, cytosolic flavo-protein that has been shown to protect cells against the toxicity of quinones and their metabolic precursors (Kappus and Sies, 1981). Thus, the studies we report here have investigated susceptibility to quinone-generating metabolites of benzene and QR activity in cultured bone marrow stromal cells derived from DBA/2 mice.

Keywords

Bone Marrow Stromal Cell Quinone Reductase Bone Marrow Stroma Benzene Metabolite Target Organ Specificity 
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.

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Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Lorraine E. Twerdok
    • 1
  • Michael A. Trush
    • 1
  1. 1.Department of Environmental Health Sciences, Division of Toxicological SciencesJohns Hopkins University School of Hygiene and Public HealthBaltimoreUSA

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