Diol epoxide adducts

As described earlier in Chapter 2, B[a]P is metabolized mainly to the 7R 7.8-transdihvdrodiol. However, both enantiomers are further epoxidized on the lower face of the molecule. Thus, while the 7R enantiomer forms mainly the anti-diol epoxide, the 7S enantiomer forms mainly svn-diol epoxide. In some systems, such as human colon (138) or hamster embryo cells (139), significant quantities of svn-diol epoxide adducts are found, including adducts... 

In the case of 7-methyl-B[a]A (155) and 7,12-dimethyl-B(a]A (DMBA) (50,55,57,156-158) most of the evidence supports bay region diol epoxide adducts. Thus, fluorescence studies (50,55,56,159), light sensitivity of the adducts (160), and analysis of adducts formed by further oxidations of the 3,4-dihydrodiol all suggest a bay region diol epoxide intermediate (161,162). More recent evidence... 

A. Harsch, J. M. Sayer, D. M. Jerina, P. Vouros, HPLC-MS/MS Identification of the Positionally Isomeric Benzo[c]phenanthrene Diol Epoxide Adducts in Duplex DNA , Chem. Res. Toxicol. 2000, 13, 1342 - 1348. 

Ling, H., Sayer, J. M., Plosky, B. S., Yagi, H., Boudsocq, F., Woodgate, R.,Jerina, D. M., and Yang, W. (2004). Crystal struc ture of a benzo [a] pyrene diol epoxide adduct in a ternary complex with a DNA polymerase. Proc. Natl. Acad. Sci. USA 101, 2265-2269. 

A 3.1 A crystal structure of human topoisomerase I in complex with DNA containing 8-oxo-dG at the +1 position in the scissile strand shows the enzyme active site to be rearranged into an inactive conformation." A primer-template duplex in complex with the lesion-bypass polymerase Dpo4 is studied in which there is a benzo[a]pyrene diol epoxide adduct of dA (183) base paired with thymidine in the enzyme active site. Two conformations of the adduct are observed, one in which it is intercalated between base pairs, and the other in... 

Day BW, Skipper PL, Wishnok JS, et al. 1990. Identification of an in v/Vo chrysene diol epoxide adduct in human hemoglobin. Chem Res Toxicol 3(4) 340-343. 

Barry, J.P., C. Norwood, and P. Vouros. 1996. Detection and identification of ben-zo[fl]pyrene diol epoxide adducts to DNA utilizing capillary electrophoresis-electrospray mass spectrometry. Anal. Chem. 68 1432-1438. 

Batra, V.K., Shock, D.D., Prasad, R., Beard, W.A., Hou, E.W., Pedersen, L.C., Sayer, J.M., Yagi, H., Kumar, S., Jerina, D.M., et al. (2006) Structure of DNA polymerase P with a benzo[c]phenan-threne diol epoxide-adducted template exhibits mutagenic features. Proc. Natl. Acad. Sci. USA, 103,17231-17236. 

Tan, J., Geacintov, N.E., and Broyde, S. (2000) Conformational determinants of structures in stereoisomeric cis-opened anti-benzo[a]pyrene diol epoxide adducts to adenine in DNA. Chem. Res. Toxicol, 13, 811-822. 

Remington, K.M., Bennett, S.E., Harris, C.M., Harris, T.M., and Bebenek, K. (1998) Highly mutagenic bypass synthesis by T7 RNA polymerase of site-specific benzo[a]pyrene diol epoxide-adducted template DNA. J. Biol. Chem., ITS, 13170-13176. 

Brylawski, B. P. Cordeiro-Stone, M. KauBnan, D. G. Ferritin-labeled rabbit Fab fragments for the single-step detection of benzo-a-pyrene-diol-epoxide adducts in DNA by electron microscopy. Carcinogenesis (Lond), 10 199-202. 1989. 

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