Duke Integrated Toxicology Program
James G. Lewis, Ph.D.
Assistant Professor of Pathology
Research Areas:
Oxidative Stress
Cell and Molecular Biology
Cancer Biology (Immunotoxicity)
Education:
B.H.S., Pathology, Duke University, 1975
Ph.D., Pathology and Toxicology, Duke University, 1982
Research Description:
We are presently investigating the effects of chemicals of environmental concern on chronic inflammatory cells, macrophages. The critical nature of these cells in host resistance and the potential danger these cells pose to the host if they were to utilize their cytotoxic functions in an unregulated manner mandates that the interaction of these cells with xenobiotics be studied from two perspectives. The first, and most obvious, is the inhibition of function by chemicals and the lowering of host defenses. The second is the enhancement or deregulation of function by chemicals and the induction of tissue damage and the potentiation of carcinogenesis.
Specifically we are investigating the mechanisms by which benzene and benzene metabolites inhibit functions critical to host defense. We have shown that benzoquinone is a potent inhibitor of receptor mediated phagocytosis and tumor cell kill. Other metabolites, benzenetriol, and hydroquinone, also inhibit macrophage functions but do so in a manner suggesting that it is their autoxidation to benzoquinones that is really responsible for their toxicity. Thus, as in other systems, benzoquinone appears to be the ultimate toxic species and we are concentrating our efforts on the mechanisms by which this chemical exerts its inhibitor effects on macrophages.
We are also investigating the effects the release of toxic oxidants from macrophages has on surrounding cells in terms of the induction of DNA damage. These studies are in support of an overall model of inflammatory mechanisms involved in carcinogenesis. We are presently interested in the potential effects of released nitric oxide and released products of phagocytized metal compounds on DNA.
Selected publications:
Klan, M., Adams, D.O., and Lewis, J.G. (1990). The effects of exposure to benzene in vivo on the murine mononuclear phagocyte system. Toxicol. Appl. Pharmacol. 103: 198-205.
Manning, B.W., Adams, D.O., and Lewis, J.G. (1993). Inhibition of phagocytosis and cytoskeletal disruption by benzene metabolites in mouse macrophages. The Toxicologist 13: 349.
Contact information
(919) 684-2159