Our group is elucidating the mechanisms by which chemicals induce cancer. The research focuses on carcinogenic polycyclic aromatic hydrocarbons (PAH), widespread environmental pollutants, and how they interact with DNA to cause mutations and cancer. Specific research projects deal with the enzymes involved in activation and detoxification of PAH (especially tissue and species specific cytochrome P450 isoforms), analysis of PAH-DNA adducts by postlabeling, the role of DNA sequence and chromatin structure in PAH-DNA adduct formation, the fine structure of repair of PAH-DNA adducts, the relationship of specific PAH-DNA adducts to mutation, the role of p53 and cell cycle checkpoints in PAH-DNA damage repair, and the discovery of chemopreventive agents. All of these projects relate directly to understanding the mechanism of action of carcinogenic chemicals to which large numbers of humans are exposed and are important for risk assessment and chemoprevention.
- MAHADEVAN B, ARORA V, SCHILD LJ, KESHAVA C, CATE ML, IVERSEN PL, POIRIER MC, WESTON A, PEREIRA C, BAIRD WM. Reduction in tamoxifen-induced CYP3A2 expression and DNA adducts using antisense technology. Mol Carcinog. 2006 Feb;45(2):118-25.
- MUSAFIA-JEKNIC, T., MAHADEVAN, B., PEREIRA, C., and BAIRD, W.M. (2005) Long Term Effects of a Standardized Complex Mixture of Urban Dust Particulate on the Metabolic Activation of Carcinogenic Polycyclic Aromatic Hydrocarbons in Human Cells in Culture. Toxicol Sci. 2005 Sep 14.
- MAHADEVAN, B., LUCH, A., BRAVO, C.F., ATKIN, J., STEPPAN, L.B., PEREIRA, C., KERKVLIET, N.I., and BAIRD, W.M. (2005). Dibenzo[a,l]pyrene induced DNA adduct formation in lung tissue in vivo. Cancer Lett. 2005 Sep 8;227(1):25-32.
- MAHADEVAN, B., KESHAVA, C., MUSAFIA-JEKNIC, T., PECAJ, A., WESTON, A., and BAIRD, W.M. (2005). Altered gene expression patterns in MCF-7 cells induced by the urban dust particulate complex mixture standard reference material 1649a. Cancer Res. 2005 Feb 15;65(4):1251-8.
- BAIRD, W.M., MAHADEVAN, B. (2004). The uses of carcinogen-DNA adduct measurement in establishing mechanisms of mutagenesis and in chemoprevention. Mutation Research 547 :1-4.
- MAHADEVAN, B., DASHWOOD, W.M., LUCH, A., PEAI, A., SEIDEL, A., PERIERA, C., and BAIRD, W.M (2003). Mutations induced by (-)-anti-11R,12S-dihydrodiol 13S,14R-epoxide of dibenzo[a,l]pyrene in the coding region of the hypoxanthine phosphoribosyltransferase (Hprt) gene in Chinese hamster V79 cells. Environmental and Molecular Mutagenesis 41 :131-139.
- BUTERS, J.T.M., MAHADEVAN, B., MARTINEZ, L.Q., GONZALEZ, F.J., GREIM, H., BAIRD, W.M BAIRD and LUCH, A. (2002). Cytochrome P450 1B1 determines susceptibility to dibenzo[a,l]pyrene-induced tumor formation. Chemical Research in Toxicology. 15 :1127-1135.
- LUCH, A., MAHADEVAN, B., BAIRD, W. M., DOEHMER, J., SEIDEL, A., GLATT, H., GREIM,H., and BUTERS, J.T.M. (2002). The Role of Cytochrome P450 1B1 in Dibenzo[a,l]pyrene-induced Carcinogenesis. Polycyclic Aromatic Compounds:22 :781-789.
- BAIRD W.M., HOOVEN L.A., MAHADEVAN B., LUCH A., and SEIDEL A. (2002). Responses of human cells to PAH-induced DNA damage. Polycyclic Aromatic Compounds: 22 :771-780, 2002
- MARSTON, C. P., PERIERA, C., FERGUSON, J., FISCHER, K. HEDSTROM, O., DASHWOOD, W.-M. and BAIRD, W.M. (2001). Effect of a complex environmental mixture from coal tar containing polycyclic aromatic hydrocarbons(PAH) on the tumor-initiation, PAH-DNA binding and metabolic activation carcinogenic PAH in mouse epidermis. Carcinogenesis:22 :1077-1086.
- MAHADEVAN, B., LUCH, A., SEIDEL, A., PELLING, J.C. and BAIRD, W.M. (2001). Effects of the (-)-anti-11R,12S-dihydrodiol 13S,14R-epoxide of dibenzo[a,l]pyrene on DNA adduct formation and cell cycle arrest in human diploid fibroblasts. Carcinogenesis 22: 161-169.
- WEIMER, T.L., REDDY, A.P., HARTIG, U., ALEXANDER, D., STAMM, S.C., MILLER, M.R., BAIRD, W., HENDRICKS, J., and BAILEY, G. (2000).Influence of ß-Naphthoflavone on 7,12-Dimethylbenz(a)anthracene Metabolism, DNA Adduction, and Tumorigenicity in Rainbow Trout. Toxicol. Sci. 57, 217-228.
- LAKSHMAN,M. K..,KOLE, P.L., CHATUREVEDI, S., SSUGIER, J.H., YEH, H.J.C., GLUSKER, J.P., CARRELL, H.L., KATZ, A. K., AFSHAR, C.E., KENNISTON, G. and BAIRD, W.M. (2000). Methyl Group-Induced Helicity in1,4-Dimethylbenzo[c]phenanthrene and Its Metabolites: Synthesis, Physical, and Biological Properties. Journal of the American Chemical 122:12629-12636.
- HEIDEL, S.L., MACWILLIAMS, P.S., BAIRD, W.M., DASHWOOD, W.M., BUTERS, J.T., GONSALEZ, F.J., LARSON, M.C., CZUPRYNSKI, C.J. and JEFCOATE, C.R. (2000). Cytochrome P4501B1 mediates induction of bone marrow cytotoxicity and preleukemia cells in mice treated with 7,12-dimethylbenz[a]anthracene. Cancer Res. 60, (13) 3454-3460.
- MELENDEZ-COLON, V.J., LUCH, A., SEIDEL, A., and BAIRD, W.M. (2000). Formation of stable DNA adducts and apurinic sites upon metabolic activation of bay and fjord region polycyclic aromatic hydrocarbons in human cell cultures. Chemical Research in Toxicology, 13 (1): 10-17.
- MELENDEZ-COLON, V.J., LUCH, A., SEIDEL, A., and BAIRD, W.M. (1999) Comparison of Cytochrome P450 and Peroxidase Dependent Metabolic Activation of the Potent Carcinogen Dibenzo[a,l]pyrene in Human Cell Lines: Formation of Stable Adducts and Absence of a Detectable Increase in Apurinic Sites. Cancer Research, 59: 1412-1416.
- LUCH, A, KUDLA, K., SEIDEL, A., DOEHMER, J., GREIM, H., and BAIRD, W.M. (1999). The level of DNA modification by (+)-syn-(11S,12R,13S,14R)- and (-)-anti-(11R,12S,13S,14R)-dihydrodiol epoxides of dibenzo[a,l]pyrene determined the effect on the proteins p53 and p21WAF1 in the human mammary carcinoma cell line MCF-7. Carcinogenesis, 20, 859-865.
- REDDY, A.P., HARTTIG, U., BARTH, M.C., BAIRD, W.M., SCHIMERLIK, M., HENDRICKS, J.D., and BAILEY, G.S. (1999). Inhibition of dibenzo[a,l]pyrene-induced multi-organ carcinogenesis by dietary chlorophyllin in rainbow trout. Carcinogenesis. 20(10):1919-26.
- LUCH, A., COFFING, S.L., TANG, Y.M., SCHNEIDER, A., SOBALLA, V., GREIM, H., JEFCOATE, C.R., SEIDEL, A., GREENLEE, W.F., BAIRD, W.M., and DOEHMER, J. (1998). Stable expression of human cytochrome P450 1B1 in V79 Chinese hamster cells and metabolically catalyzed DNA adduct formation of dibenzo[a,l]pyrene. Chemical Research in Toxicology, 11 (6): 686-695.
- MELENDEZ-COLON, V.J., SMITH, C.A., SEIDEL, A., LUCH, A., PLATT, K.L. and BAIRD, W.M. (1997). Formation of stable adducts and absence of depurinating DNA adducts in cells and DNA treated with the potent carcinogen dibenzo[a,l]pyrene or its diol epoxides. Proceedings of the National Academy of Sciences, U.S.A, 94: 13542-13547.