The research in my program involves the development and application of molecular biomarkers of exposure, dose, and effect from environmental carcinogens. The environmental carcinogens studied include agents that are naturally occurring in the diet as well as those produced as a result of cooking practices. A major emphasis of the research has been in the elucidation of the role of aflatoxins, a common contaminate of the food supply, in the induction of liver cancer in high-risk populations living in Asia and Africa. This work has led to the identification of a very strong chemical-viral interaction between aflatoxin and the human hepatitis B virus in the induction of liver cancer. These biomarkers have also been used in many collaborative molecular epidemiology studies of liver cancer risk and recently employed to assess the efficacy of a number of chemopreventive agents in trials in high-risk aflatoxin-hepatitis B virus exposed populations. This research is now being extended to develop genetic biomarkers of p53 mutations and viral alterations in human samples as early detection of disease biomarkers using a novel mass spectroscopy based method for genotyping developed in the laboratory. Thus, the research in our laboratory focuses on the translation of mechanistic research to public health based prevention strategies.

Environmental Health Sciences, Chemical carcinogenesis; environmental carcinogenesis; chemoprevention; cancer prevention and control

National Cancer Institute Research Career Development Award

Delta Omega Honor Society in Public Health, Alpha Chapter

Phi Beta Kappa

Yuan, JM, Ambinder, A., Fan, YH, Gao, YT, Yu, MC and Groopman, JD. Prospective evaluation of hepatitis B 1762T/1764A mutations on hepatocellular carcinoma development in Shanghai, China. Cancer Epidemiology,Biomarkers and Prevention, 18:590-594, 2009.

Bransfield, L.A., Rennie, A., Visvanathan, K., Odwin, S.A., Kensler, T.W., Yager, J.D., Friesen, M.D. and Groopman, J.D. Formation of Two Novel Estrogen Guanine Adducts and HPLC/MS Detection of 4-Hydroxyestradiol-N7-Guanine in Human Urine. Chemical Research in Toxicology, 21:1622-30, 2008.

Egner, P. A., Kensler, T.W., Chen, J-G, Gange, S., Groopman, J.D. and Friesen, M.A. Quantification of Sulforaphane Mercapturic Acid Pathway Conjugates in Human Urine by High-Performance Liquid Chromatography and Isotope-Dilution Tandem Mass Spectrometry. Chemical Research in Toxicology, 21:1991-1996, 2008.

Roebuck, BD, Johnson, DN, Sutter, CH, Egner, PA, Scholl, PF, Friesen, MD, Baumgartner, KJ, Ware, NM, Bodreddigari, S, Groopman, JD, Kensler, TW and Sutter, TR. Transgenic expression of aflatoxin aldehyde reductase (AKR7A1) modulates aflatoxin B1 metabolism but not hepatic carcinogenesis in the rat. Toxicological Sciences, in press.

Liby, K., Yore, M., Roebuck, B.D., Baumgartner, K.J., Honda, T., Sundararajan, C., Yoshizawa, H., Gribble, G.W., Williams, C.R., Risingsong, R., Royce, D.B., Dinkova-Kostova, A.T., Stephenson, K.K., Egner, P.A., Yates, M.S., Groopman, J.D., Kensler, T.W. and Sporn, M.B. A novel acetylenic tricyclic bis-(cyano enone) potently induces phase 2 cytoprotective pathways and blocks liver carcinogenesis induced by aflatoxin. Cancer Research, 68:6727-6733, 2008.

Johnson, DN, Egner, PA, OBrian, G, Glassbrook, N, Roebuck, BD, Sutter, T, Payne, GA, Kensler, TW, and Groopman, JD. Quantification of Urinary Aflatoxin B1 Dialdehyde Metabolites Formed by Aflatoxin Aldehyde Reductase Using Isotope Dilution Tandem Mass Spectrometry. Chemical Research in Toxicology 21:752-760, 2008.

Scholl, P.F. and Groopman, J.D. Long Term Stability of Human Aflatoxin B1 Albumin Adducts Assessed by Isotope Dilution Mass Spectrometry and HPLC-Fluorescence. Cancer Epidemiology, Biomarkers and Prevention 17: 1436-1439, 2008.

Bodreddigari, S.,Jones, L.,Groopman, J., Sutter, C., Roebuck, B., Guengerich, F. Kensler, T. , and Sutter, T. Protection Against Aflatoxin B1-induced Cytotoxicity by Expression of the Cloned Aflatoxin B1-aldehyde Reductases Rat AKR7A1 and Human AKR7A3. Chemical Research in Toxicology 21:1134-42, 2008.

McCoy, L.F, Scholl, P.F., Sutcliffe, A.E., Kieszak , S.M., Powers, C.D., Rogers, H.S., Gong, YY, Groopman, J.D., Wild, C.P. and Schleicher, R.L. Human Aflatoxin Albumin Adducts Quantitatively Compared by ELISA, HPLC with Fluorescence Detection and HPLC with Isotope Dilution Mass Spectrometry. Cancer Epidemiology, Biomarkers and Prevention 17, 1653-1657, 2008.

Chen, JC, Kuang, SY, Egner, PA, Lu, JH, Zhu, YR, Wang, JB, Zhang, BC,Chen, TY, Muñoz, A, Kensler, TW and Groopman, JD. Acceleration To Death From Liver Cancer In People With Hepatitis B Viral Mutations Detected In Plasma By Mass Spectrometry. Cancer Epidemiology, Biomarkers and Prevention 16:1213-1218, 2007.

Everley, RA, Ciner, FL, Zhang, D, Scholl, PF, Groopman, JD and Croley, TR. Measurement of Aflatoxin and Aflatoxin Metabolites in Urine by Liquid Chromatography Tandem Mass Spectrometry. Journal of Analytical Toxicology 31:150-156, 2007.

Simonich, MT, Egner, PA, Roebuck, BD, Orner, G, Jubert, C, Pereira, C, Groopman, JD, Kensler, TW, Dashwood, RH, Williams, D, and Bailey, GS. Natural chlorophyll inhibits aflatoxin B1 induced multi-organ carcinogenesis in the rat. Carcinogenesis 28:1294-1302, 2007.

Skipper, PL, Trudel, LJ, Kensler, TW, Groopman, JD, Egner, PA, Liberman, RG, Wogan, GN and Tannenbaum, SR. DNA adduct formation by 2,6-dimethyl-, 3,5-dimethyl-, and 3-ethylaniline in vivo in mice. Chemical Research in Toxicology 19:1086-90, 2006.

Egner, P. Groopman, J.D., Wang, J-S, Kensler, TW and Friesen, MD. Quantification of Aflatoxin-B1-N7-guanine in Human Urine by High-Performance Liquid Chromatography and Isotope-Dilution Tandem Mass Spectrometry, Chemical Research in Toxicology 19:1191-1195, 2006.

Yates, MS, Kwak, MK, Egner, PA, Groopman, JD, Baumgartner, K., Roebuck, BD, Yore, M, Honda, T., Gribble, GW, Sporn, MB and Kensler, TW. Potent Protection against Aflatoxin-Induced Tumorigenesis through Induction of Nrf2-Regulated Pathways by the Synthetic Triterpenoid, CDDO-Imidazole. Cancer Research 66:2488-2494, 2006.

Scholl, PF, McCoy, L, Kensler, TW and Groopman, JD. Quantitative Analysis of Aflatoxin B1 Quantitative Analysis and Chronic Dosimetry of Aflatoxin B1 Plasma Albumin Adducts in Rats by HPLC-Electrospray Mass Spectrometry. Chemical Research in Toxicology 19:44-9, 2006.

Sapkota, A., Halden, R.U., Dominici, F., Groopman, J.D. and Buckley, T. Exposure Characterization and Biomarker Evaluation of 1,3-Butadiene Resulting from Mobile Sources. Chemical and Biological Interactions 160:70-79, 2006.

Scholl P.F., Turner P.C., Sutcliffe A.E, Sylla A., Diallo M.S., Friesen M.D., Groopman J.D., and Wild C.P. Quantitative Comparison of Aflatoxin B1 Serum Albumin Adducts in Humans by Isotope Dilution Mass Spectrometry and Enzyme Linked Immunosorbent Assay. Cancer Epidemiology, Biomarkers and Prevention 15: 823-6, 2006.

Strosnider, H, Azziz-Baumgartner, E., Banziger, M., Bhat, RV., Breiman, R., Brune, MN, DeCock, K., Dilley, A., Groopman, J., Hell, K., Henry, SH., Jeffers, D., Jolly, C., Jolly, P., Kibata, GN, Lewis, L., Liu, XM, Luber, G., McCoy, L., Mensah, P., Miraglia, M., Misore, A., Njapau, H., Ong, CN, Onsongo, M., Page, SW., Park, D., Patel, M., Phillips, T., Pineiro, M., Pronczuk, J., Rogers, HS, Rubin, C. Sabino, M., Schaafsma, A., Shephard, G., Stroka, J., Wild, C., Williams, JT and Wilson, D. Public Health Strategies for Reducing Aflatoxin Exposure in Developing Countries. Environmental Health Perspectives 114:1898–1903, 2006.

Kuang, SY, Lekawanvijit, S, Maneekarn, N, Thongsawat, S, Brodovicz, K, Nelson, K and Groopman, JD. Hepatitis B 1762T/1764A Mutations, Hepatitis C Infection and Codon 249 p53 Mutations In Hepatocellular Carcinomas From Thailand. Cancer Epidemiology, Biomarkers and Prevention 14:380-384, 2005.

Kensler, T.W., Chen, J-G., Egner, P.A., Fahey, J.W., Jacobson, L.P., Stephenson, K.K., Ye, X., Coady, J.L.,Wang, J-B., Wu, Y., Sun, Y., Zhang, Q-N., Zhang, B-C., Zhu, Y-R., Qian, G-S., Carmella, S.G., Hecht, S.S., Benning, L., Gange, S.J., Groopman, J.D. and Talalay, P. Effects of glucosinolate-rich broccoli sprouts on urinary levels of aflatoxin-DNA adducts and phenanthene tetraols in a randomized clinical trial in He Zuo Township, Qidong, PRC. Cancer Epidemiology, Biomarkers and Prevention 14: 2605-13, 2005.

Lleonart, ME, Kirk, G, Villar, S, Lesi, OA, Dasgupta, A, Goedert, JJ, Mendy, M, Hollstein, MC, Montesano, R, Groopman, JD, Hainaut, P., and Friesen, MD. Quantitative Analysis of Plasma TP53 249Ser-Mutated DNA by Electrospray Ionization Mass Spectrometry in Liver Cancer. Cancer Epidemiology, Biomarkers and Prevention 14: 2956-62, 2005.