Environmental & Molecular Toxicology

David Williams

Professor Director
Dept: EMT (435 Weniger Hall)
Director: NIEHS Marine/Freshwater Biomedical Sciences Center
Ph.D. 1982 Oregon State University
Phone: 541-737-3277
Fax: 541-737-7966
david.williams@oregonstate.edu

My research interests are in the characterization and regulation of microsomal monooxygenase enzymes (Cytochromes P450 and Flavin-Containing Monooxygenases) active in drug metabolism and their involvement in the detoxication and/or bioactivation of drugs, xenobiotics and endogenous compounds. In addition, a major focus of current research efforts is on diet and cancer.  These studies employ both trout, mouse and human cell culture models to address mechanistic questions.  Currently, we are working on a model that addresses the issue of maternal diet on cancer risk for the fetus in later life.  I am an Investigator in The Linus Pauling Institute and the Marine and Freshwater Biomedical Sciences Center.

Selected Publications:

• Yu Z, Loehr CV, Fischer KA, Louderback MA, Krueger SK, Dashwood RH, Kerkvliet NI, Pereira CB, Jennings-Gee JE, Dance ST, Miller MS, Bailey GS, and Williams DE (2006) In utero exposure of mice to dibenzo[a,l]pyrene produces lymphoma in the offspring: role of the aryl hydrocarbon receptor. Cancer Res. 66(2):755-62.
• Tilton, S.C., Givan, S.A., Pereira, C.B., Bailey, G.S., and Williams, D.E. (2005) Toxicogenomic Profiling of the Hepatic Tumor Promoters Indole-3-Carbinol, 17{beta}-estradiol and {beta}-naphthoflavone in Rainbow Trout. Toxicol Sci. [Epub ahead of print].
• Tilton, S.C., Gerwick, L.G., Hendricks, J.D., Rosato, C.S., Corley-Smith, G., Givan, S.A., Bailey, G.S., Bayne, C.J., and Williams, D.E. (2005). Use of a rainbow trout oligonucleotide microarray to determine transcriptional patterns in aflatoxin B1-induced hepatocellular carcinoma compared to adjacent liver. Toxicol Sci. 88(2):319-30.
  
• Krueger, S.K. and Williams, D.E. (2005) Mammalian Flavin-Containing Monooxygenases: Structure/Function, Genetic Polymorphisms and Role in Drug Metabolism. Pharmacol. Therap. 106:357-387.
  
• Krueger, S.K., Siddens, L.K., Henderson, M.C., Andreasen, E.A., Tanguay, R.L., Pereira, C.B., Cabacungan, E.T., Hines, R.N., Ardlie, K. and Williams, D.E. (2005) Haplotype and Functional Analysis of Four Flavin-Containing Monooxygenase Isoform 2 (FMO2) Polymorphisms in Hispanics. Pharmacogenetics and Genomics. 15:245-256.
  
• Traber, M.G., Siddens, L.K., Leonard, S.W., Schock, B., Gohil, K., Krueger, S.K., Cross, C.E. and Williams, D.E. (2005). Alpha-tocopherol modulates Cyp3a expression, increases gamma-CEHC production, and limits tissue gamma-tocopherol accumulation in mice fed high gamma-tocopherol diets. Free Rad. Biol. Med. 38:773-785.
  
• Krueger, S.K., Siddens, L.K., Martin, S.R., Yu, A., Pereira, C.B., Cabacungan, E.T., Hines, R.N., Ardlie, K.G., Raucy, J.L. and Williams, D.E. (2004) Differences in FMO2*1 Allelic Frequency Between Hispanics of Puerto Rican and Mexican Descent. Drug Metabol. Dispos. 32:1337-1340.
  
• Henderson, M.C., Krueger, S.K., Siddens, L.K, Stevens, J.F. and Williams, D.E. (2004) S-Oxygenation of the Thioether Organophosphate Insecticides Phorate and Disulfoton by Human Lung Flavin-Containing Monooxygenase 2. Biochem. Pharmacol. 68:959-967.
  
• Henderson, M.C., Krueger, S.K., Stevens, J.F. and Williams, D.E. (2004) Human flavin-containing monooxygenase form 2 S-oxygenation: sulfenic acid formation from thioureas and oxidation of glutathione. Chem. Res. Toxicol. 17:633-640.
  
• Mata, J.E., Yu, Z., Gray, J.E., Williams, D.E. and Rodriguez-Proteau, R. (2004) Effects of Chlorophyllin on Transport of Dibenzo(a,l)pyrene, 2 Amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine, and Aflatoxin B1 across Caco-2 cell monolayers. Toxicology. 196:117-125.
  
• William, D.E., Bailey, G.S., Reddy, A., Hendricks, J.D., Oganesian, A., Orner, G.A., Pereira, C.B., and Swenberg, J.A. (2003). The rainbow trout (Oncorhynchus mykiss) tumor model: recent applications in low-dose exposures to tumor initiators and promoters. Toxicol Pathol. 2003 Jan-Feb;31 Suppl:58-61.
  
• Leibelt, D.A., Hedstrom, O.R., Fischer, K.A., Pereira, C.B. and Williams, D.E. (2003) Evaluation of Chronic Dietary Exposure to Indole-3-Carbinol and Absorption-Enhanced 3,3'-Diindolylmethane in Sprague-Dawley Rats. Toxicol. Sci.,74:10-21.
  
• Krueger, S.K., Williams, D.E., Yueh, M.-F., Martin, S.R., Hines, R.N., Raucy, J.L., Dolphin, C.T., Shephard, E.A. and Phillips, I.R. (2002) Genetic Polymorphisms of Flavin-Containing Monooxygenase (FMO). Drug Metabol. Rev. 34:523-532.
  
• Krueger, S.K., Martin, S.R., Yueh, M.-F., Pereira, C.B. and Williams, D.E. (2002) Identification of Active Flavin-Containing Monooxygenase Isoform 2 in Human Lung and Characterization of Expressed Protein. Drug Metabol. Dispos. 30:34-41.
  
• Larsen-Su, S. and Williams, D.E. (2001) Transplacental Exposure to Indole-3-Carbinol Induces Sex-Specific Expression of CYP1A1 and CYP1B1 in the Liver of Fischer 344 Neonatal Rats. Toxicol. Sci., 64:162-168.
  
• Shilling, A.D., Carlson, D.B., Katchamart, S. and Williams, D.E. (2001) 3,3'-Diindolylmethane, a Major Condensation Product of Indole-3-Carbinol, is a Potent Estrogen in the Rainbow Trout. Toxicol. Appl. Pharmacol. 170:191-200.
  
• Carlson, D.B., and Williams, D.E. (2001) 4-hydroxy-2',4',6'-trichlorobiphenyl and 4-hydroxy-2',3',4',5'-tetrachlorobiphenyl are estrogenic in rainbow trout. Environ. Toxicol. Chem. 20:351-358.
  
• Shilling, A.D. and Williams, D.E. (2000) The Non-Aromatizable Androgen, Dihydrotestosterone, Induces Antiestrogenic Responses in the Rainbow Trout. J. Steroid Biochem. Molec. Biol. 74:187-194.
  
• Whestine, J.R., Yueh, M.-F., Hopp, K.A., McCarver, D.G., Williams, D.E., Park, C.-S., Kang, J.H., Cha, Y.-N., Dolphin, C.T., Shephard, E.A., Phillips, I.R. and Hines, R.N. (2000) Ethnic Differences in Human Flavin-Containing Monooxygenase 2 (FMO2) Polymorphisms: Detection of Expressed Protein in African Americans. Toxicol. Appl. Pharmacol. 168:216-224.
  
• Shilling, A.D. and Williams, D.E. (2000) Determining Relative Estrogenicity by Quantifying Vitellogenin Induction in Rainbow Trout Liver Slices. Toxicol. Appl. Pharmacol. 164:330-335.
  
• Carlson, D.B., Curtis, L.R. and Williams, D.E. (2000) Salmonid Sexual Development is not Consistently Altered by Embryonic Exposure to Endocrine-Active Chemicals. Environm. Hlth. Perspect. 108:249-255.
  
• Oganesian, A., Hendricks, J.D., Pereira, C.B., Orner, G.A., Bailey, G.S., and Williams, D.E. (1999). Potency of dietary indole-3-carbinol as a promoter of aflatoxin B1-initiated hepatocarcinogenesis: results from a 9000 animal tumor study. Carcinogenesis. 20(3):453-8.
  
• Orner, G.A., Hendricks, J.D., Arbogast, D. and Williams D.E. (1998). Modulation of aflaxtoxin B1 heptacarcinogenesis in trout by dehydroepiandrosterone:  Initiation/post-initiation and latency effects. Carcinogenesis 19,161-167.
  
• Cheng, R., Bradford, S., Barnes, D., Williams, D.E., Hendricks, J. and Bailey, G. (1997). Cloning, sequencing, and embryonic expression of an N-ras proto-oncogene isolated from an enriched zebrafish (Danio rerio) cDNA library.  Mol. Mar. Biol. Biotech. 6(1), 40-47.