Research Program: Carcinogenesis & Chemoprevention
Associate Professor, Department of Medicinal Chemistry

trety001@umn.edu
612-626-3432 — office
612-624-0638 — lab
Preferred method of contact: e-mail

• B.Sc., Moscow State University, Russia, 1988
• M.S., Moscow State University, Russia, 1990
• Ph.D., University of North Carolina at Chapel Hill, 1997
• Postdoctoral, Massachusetts Institute of Technology, 1999

Research Interests

Humans are exposed to complex mixtures of environmental and dietary carcinogens, as well as endogenous electrophiles produced from normal metabolism. Some of these chemicals and their metabolites are electrophilic species capable of chemical reactions with DNA. The resulting covalently modified DNA nucleobases (DNA adducts) have distorted base pairing characteristics and, if not repaired, can be converted to heritable mutations during DNA replication. Carcinogen-induced changes in critical genes that control cell growth and differentiation can lead to the initiation of cancer. Paradoxically, many common antitumor drugs use a similar mechanism by alkylating DNA in an attempt to induce tumor cell death. Long-term cancer survivors are at risk for secondary cancers resulting from exposure to antineoplastic agents. The focus of our research is to investigate the structural basis for promutagenic and anticancer activity of DNA-modifying agents. The primary experimental tool employed in our laboratory is biological mass spectrometry (ESI-MS, cap HPLC-MS, MS/MS, and MALDI-TOF MS), although most of the projects also involve organic synthesis, structural analyses (e.g. NMR, 2D NMR, CD spectroscopy), and molecular modeling of chemically altered DNA.

For a more detailed description of Dr. Tretyakova's research interests, please visit her Department of Medicinal Chemistry Web site.

Selected Publications

Tretyakova, N.Y., Livshits, A., Park, S., Bisht, B., and Goggin, M. (2007) Structural elucidation of a novel DNA-DNA cross-link of 1,2,3,4-diepoxybutane. Chem. Res. Toxicol., 20, 284-289.

Antsypovich, S., Quirk Dorr, D., Pitts, C., and Tretyakova, N.Y. (2007) Site specific N⁶-(2-hydroxy-3,4-epoxybut-1-yl)adenine oligodeoxynucleotide adducts of 1,2,3,4 diepoxybutane: synthesis and stability at physiological pH. Chem. Res. Toxicol., 20, 641-649.

Kim, M.Y., Park, S., Tretyakova, N.Y., and Wogan, G. (2007) Mutagenesis of the supF gene by stereoisomers of 1,2,3,4-diepoxybutane. Chem. Res. Toxicol., 20, 790-797.

Goggin, M., Loeber, R., Park, S., and Tretyakova, N.Y. (2007) HPLC-ESI⁺-MS/MS analysis of N7-guanine-N7-guanine DNA cross-links in tissues of mice exposed to 1,3-butadiene. Chem. Res. Toxicol., 20, 839-847

Miksa, B., Chinnapann, R., Dang, N.C., Reppert, M., Matter, B., Tretyakova, N.Y., Grubor, N., and Jankowiak, R. (2007) Spectral differentiation and immunoaffinity capillary electrophoresis separation of enantiomeric benzo(a)pyrene diol epoxide-derived DNA adducts. Chem. Res. Toxicol. 20, 1192-1199.

Matter, B., Guza, R., Zhao, J., Li, Z., Jones, R., and Tretyakova, N.Y. (2007) Sequence distribution of acetaldehyde-derived N²-ethyl-dG adducts along duplex DNA. Chem. Res. Toxicol. 20, 1379-1387.

Quirk-Dorr, D., Murphy, K., and Tretyakova, N.Y. (2007) Synthesis of DNA oligodeoxynucleotides containing structurally defined N⁶ -(2'-hydroxy-3',4'-buten-1'-yl)-adenine adducts of 3,4-epoxy-1-butene. Chemico-Biol. Interact. 166, 104-111.

Loeber, R., Michaelson, E., Fang, Q., Campbell, C., Pegg, A.E., and Tretyakova, N.Y. (2008) Cross-linking of the DNA repair protein O⁶-alkylguanine DNA alkyltransferase to DNA in the presence of antitumor nitrogen mustards. Chem. Res. Toxicol. 21, 787-795.

Goggin, M., Anderson, C., Park, S., Walker, V., and Tretyakova, N.Y. (2008) Quantitative HPLC-ESI⁺ MS/MS analysis of adenine-guanine cross-links of 1,2,3,4-diepoxybutane in vitro and in vivo. Chem. Res. Toxicol., 21, 1163-70.

Tretyakova, N.Y., Guza, R., and Matter, B. (2008) Endogenous cytosine methylation and the formation of carcinogen carcinogen-DNA adducts. Nucleic Acids Symp. Ser. 52, 49-50.

Goggin, M., Swenberg, J.A., Walker, V., and Tretyakova, N.Y. (2009) Molecular dosimetry of 1,2,3,4-diepoxybutane-induced DNA-DNA cross-links in B6C3F1 mice and F344 rats exposed to 1,3-butadiene by inhalation. Cancer Res. 69, 2479-2486.

Loeber, R.L., Michaelson-Richie, E.D., Codreanu, S.G., Liebler, D.C., Campbell, C.R., Tretyakova, N.Y. (2009) Proteomic analysis of DNA-protein cross-linking by antitumor nitrogen mustards. Chem. Res. Toxicol. 22, 1151-1162. 

Guza, R., Ma, L., Fang, Q., Pegg, A.E., and Tretyakova, N.Y. (2009) Cytosine methylation effects on the repair of O⁶-methylgunaines within CG dinucleotides. J. Biol. Chem. Epub ahead of print 15-Jun-2009

Moser, A., Guza, B., Tretyakova, N.Y., and York, D. (2009) Density functional study of the influence of C5 cytosine substitution in base pairs with guanine. Theor. Chem. Accounts. 122, 179-188.