ROLE OF NITRIC-OXIDE IN HEMATOSUPPRESSION AND BENZENE-INDUCED TOXICITY

It is becoming increasingly apparent that nitric oxide plays a multifu nctional role in regulating inflammatory processes in the body. Althou gh nitric oxide and its oxidation products are cytotoxic toward certai n pathogens, they can also cause tissue injury and suppress proliferat ion. Cytokines and growth factors released at sites of inflammation or injury stimulate both immune and nonimmune cells to produce nitric ox ide. Nowhere in the body is this more detrimental than in the bone mar row, for the continuous production of hematopoietic precursors is esse ntial for normal blood cell maturation. Our laboratories have discover ed that, in response to inflammatory mediators, bone marrow cells read ily produce nitric oxide. Nitric oxide production is enhanced by hemat opoietic growth factors including interleukin-3, macrophage colony sti mulating factor, and granulocyte-macrophage colony-stimulating factor. When bone marrow cells produce nitric oxide, hematopoiesis is impaire d, an effect that is potentiated by colony-stimulating factors. Treatm ent of mice with benzene, which suppresses bone marrow cell developmen t, was found to markedly enhance the ability of bone marrow cells to p roduce nitric oxide in response to inflammatory mediators alone and in combination with hematopoietic growth factors. Taken together, these data suggest that nitric oxide may be an important mediator of benzene -induced bone marrow suppression.