Environmental & Molecular Toxicology

Donald Buhler

Professor Emeritus
Dept: EMT (351 Weniger Hall)
Ph.D., 1956, Oregon State College
Phone: 541-737-9036
Fax: 541-737-0497
Donald.Buhler@oregonstate.edu

My research program is primarily concerned with the biochemical effects, mechanisms for toxicity and biotransformation of environmental contaminants and other toxic chemicals. Since most chemicals either are either detoxified or are converted to more toxic metabolites in vivo, we are especially interested in studying the types of metabolic transformations that occur and the enzymes, especially the cytochromes P450, involved in these processes, and the biochemical consequences of such metabolism. Related research focuses on the regulation of cytochrome P450 expression and on the initiation phases of chemical carcinogenesis. Other research is examining the promising anticancer and antioxidant properties of flavonoids and chalcones from the hops (Humulus lupulus) plants. Studies in different test systems are underway to determine the effects and possible mechanisms of action of several hop chemicals constituents for both cancer chemoprevention, for cancer chemotherapy and for treatment or protection against cardiovascular disease. Exploratory research also is being done in an attempt to develop sensitive biomarkers for exposure to endocrine disruptors and other environmental chemicals.

• YIN H.C., TSENG H.P., CHUNG H.Y., KO C.Y., TZOU W.S., BUHLER D.R. and HU C.H.  (2008).  Influence of TCDD on zebrafish CYP1B1 transcription during development.  Toxicol. Sci. 103, 158-168. 
• TIMME-LARAGY A.R., NOYES P.D., BUHLER D.R., and DI GIULIO R.T.  (2008).  CYP1B1 knockdown does not alter synergistic developmental toxicity of polycyclic aromatic hydrocarbons in zebrafish (Danio rerio).  Mar Environ Res. Feb 26; [Epub ahead of print].
• WANG-BUHLER, J.-L., LEE, S.G., CHUNG, W.G., STEVENS, J.F., TSENG, H.P., HSU, T.H., HU, C.H., WESTERFIELD, M.,YANG, Y.-H., MIRANDA, C.L. and BUHLER, D.R. (2005). CYP2K6 from zebrafish (Danio rerio): Cloning, mapping, developmental/tissue expression, and aflatoxin B1 activation by baculovirus expressed enzyme. Comp. Biochem. Physiol., Part C 140, 207-219.
• TSENG, H.-P., HSU, T.-H., BUHLER, D.R. and HU, C.-H. (2005). Constitutive and xenobiotic-induced expression of a novel CYP3A gene from zebrafish larva. Toxicol. Appl. Pharmacol. 205, 247-258.
• MIRANDA, C.L., BUHLER, D.R., LIANG, A., DEINZER, M.L., TAYLOR, A.W., STEVENS, J.F., BOMBEN, V and BECKMAN, J.S. (2005). Hop proanthocyanidins protect against SIN-1-induced cytotoxicity in PC12 cells. Acta Hort. (ISHS) 668, 207-212.
• GROSS-STEINMEYER, K., STAPELTON, P.L., LIU, F., TRACY, J.H., BAMMLER, T.K., QUIGLEY, S.D., FARIN, F.M., BUHLER, D.R., SAFE, S.H., STROM, S.C. and EATON, D.L. (2004). Phytochemical-induced changes in gene expression of carcinogen-metabolizing enzymes in cultured human primary hepatocytes. Xenobiotica 34, 619-632.
• CHUNG, W.-G., SEN, A., WANG-BUHLER, J.-L., YANG, Y.-H., LOPEZ, N., MERRILL, G.F., MIRANDA, C.L. HU, C.-H. and BUHLER, D.R. (2004). cDNA-directed expression of a functional zebrafish CYP1A1 in yeast. Aquatic Toxicol. 70, 111-121.
• DURINGER, J.M., BUHLER, D.R. and CRAIG A.M. (2004). Comparison of hepatic in vitro metabolism of the pyrrolizidine alkaloid senecionine in sheep and cattle. Am. J. Vet. Res. 65, 1563-1572.
• WANG, W.-D., WANG, Y., WEN, H.-J., BUHLER, D.R. and HU, C.-H. (2004) . Phenylthiourea as a weak activator of aryl hydrocarbon receptor inhibiting 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced CYP1A1 transcription in zebrafish embryos. Biochem. Pharmacol. 68, 63-71.
• CHUNG, W.-G. and BUHLER, D.R. (2004). Differential metabolism of the pyrrolizidine alkaloid, senecionine, in Fischer 344 and Sprague-Dawley rats. Arch Pharmacal. Res. 27, 547-553.
• YILMAZER, M., STEVENS, J.F., DEINZER, M.L. and BUHLER, D.R. (2001). In vitro biotransformation of xanthohumol, a flavonoid from hops (Humulus lupulus), by rat liver microsomes. Drug Metab. Dispos. 29, 223-231.
• YANG, Y.-H., MIRANDA, C. L., HENDERSON, M.C., WANG-BUHLER, J.-L. and BUHLER, D.R. (2000). Heterologous expression of CYP2K1 and identification of the expressed protein (BV-CYP2K1) as lauric acid (Omega-1) hydroxylase and aflatoxin B1 exo-epoxidase. Drug Metab. Dispos. 28, 1279-1283.
• BUHLER, D.R., MIRANDA, C.L., HENDERSON, M.C., YANG, Y.-H., LEE, S.-J., and WANG-BUHLER, J.-L. (2000) Effects of 17ß-estradiol and testosterone on hepatic mRNA/protein levels and catalytic activities of CYP2K1, CYP2M1 and CYP3A27 in rainbow trout (Oncorhynchus mykiss). Toxicol. Appl. Pharmacol. 168, 91-101.
• MIRANDA, C.L., STEVENS, J.F., IVANOV, V., MCCALL, M., FREI, B., DEINZER, M.L. and BUHLER, D.R. (2000). Antioxidant and prooxidant actions of prenylated and nonprenylated chalcones and flavonoids in vitro. J. Agric. Food Chem. 48, 3876-3884.
• MIRANDA, C.L., STEVENS, J.F., HELMRICH, A., HENDERSON, M.C., RODRIGUEZ, R.J., YANG, Y.-H., DEINZER, M.L., BARNES, D.W. and BUHLER, D.R. (1999). Antiproliferative and cytotoxic effects of prenylated flavonoids from hops (Humulus lupulus) in human cancer cell lines. Food Chemical Toxicol. 37, 271-285.
• BUHLER, D.R. and WANG-BUHLER, J.-L. (1998). Rainbow trout cytochrome P450s: Purification, molecular aspects, metabolic activity, induction and role in environmental monitoring. Comp. Biochem. Physiol. Part C 121, 107-137.
• TROXEL, C.M., BUHLER, D.R., HENDRICKS, J.D. and BAILEY, G.S. (1997). CYP1A induction by Beta-naphthoflavone, Aroclor 1254 and 2,3,7,8-tetrachlorodibenzo-p-dioxin and its influence on aflaxtoxin B1 metabolism and DNA adduction in zebrafish (Danio rerio). Toxicol. Appl. Pharmacol. 146, 69-78.