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William K. Nichols

Associate Professor of Pharmacology and Toxicology

Education and Training

B.S., 1966 University of Washington, Pharmacy

Ph.D., 1971 University of Minnesota ,Pharmacology

Research Interests

My research program has included a number of biochemical and toxicological studies on hormonal and cytokine regulation of lymphocytes, macrophages and vascular endothelial cells. More recent studies have focused on mechanisms of pulmonary toxicity involving isolated lung cells and human lung cell lines. The current research efforts involve a close collaboration with Dr. Garold S. Yost, Professor, Department of Pharmacology and Toxicology, University of Utah. Our current research has utilized transfected human bronchial epithelial cell lines that overexpress specific human cytochrome P450 enzymes. These human lung cell lines have been utilized to compare the ability of specific lung cytochrome P450 enzymes to bioactivate 3-methylindole to a cytotoxic intermediate. The role of glutathione conjugation in the detoxification of 3-methylindole has also been assessed in our ongoing studies of the comparative susceptibility of lung cell subpopulations to toxicants. Some recent studies in our laboratory have demonstrated that 3-methylindole-induced cytotoxicity is linked with a cytochrome P450-mediated bioactivation that also involves an induction of apoptosis in susceptible cells. Therefore, a number of current studies include an assessment of the apoptotic pathways involved in the observed DNA fragmentation and formation of apoptotic bodies in human lung cells incubated with 3-methlyindole.

Selected Publications

Nichols, W.K., Larson, D.N. and Yost, G.S., 1990, Bioactivation of 3-methylindole by isolated lung cells, Toxicol. Appl. Pharmacol. 105:264-270.

Nichols, W.K., Covington, M.O., Seiders, C.D., Safiullah, S. and Yost, G.S., 1992, Bioactivation of halogenated hydrocarbons by rabbit pulmonary cells, Pharmacology & Toxicology 71:335-339.

Thornton-Manning J.R., Nichols, W.K., Manning, B.W., Skiles, G.L. and Yost, G.S. 1993, Metabolism and bioactivation of 3-methylindole by Clara cells, Alveolar Macrophages and Subcellular Fractions from Rabbit lungs, Toxicol. Appl. Pharmacol. 122, 182-190.

Nichols, W.K., Terry, C.M., Cutler, N.S., Appleton, M.L., Jesthi, P.K. and Yost, G.S., 1995, Oxidation of C-1 controls the cytotoxicity of 1,1-Dichloro-2,2-Bis(p-chlorophenyl)ethane by rabbit and human lung cells, Drug Metab. Dispos. 23, 595-599.

Skordos, K.W., Nichols, W.K., Pfeifer, A.M.A., and Yost, G.S., 1997, Bioactivation of 3-methylindole by human cytochrome P450 enzymes expressed in human lung cells. Toxicologist 36:26

W.K. Nichols, R. Mehta, K. Skordos, K. MaceÅå, A.M.A. Pfiefer, B.A. Carr, T. Minko, S.W. Burchiel, and G.S. Yost, 3-Methylindole-Induced toxicity to human bronchial epithelial cell lines, 2003, Tox. Sci. 71:229-236.

Pharmacology & Toxicology   College of Pharmacy   30 S. 2000 E., Rm 201, SLC  UT 84112  phone: 801-581-6287  fax: 801-585-5111 phtx@pharm.utah.edu