Benzo pyrene diol epoxides

A-Hydroxy-4- acetylaminobiphenyl Benzo [a] pyrene diol epoxide Human TK6 lymphoblastoid Custom A-Hydroxy-4- acetylaminobiphenyl 10 xMfor27h Benzo[ajpyrene diol epoxide 10 xM for Ih Gene name, gene symbol, gene bank accession fold change in a table All data available online 116... 

Luo W, Fan W, Xie H, ling L, Ricicki E, Vouros P, et al. Phenotypic anchoring of global gene expression profiles induced by A -hydroxy-4-acetylaminobiphenyl and benzo[a]pyrene diol epoxide reveals correlations between expression profiles and mechanism of toxicity. Chem Res Toxicol 2005 18 619-29. 

A Mechanism for the Stereoselectivity and Binding of Benzo[a]pyrene Diol Epoxides to DNA... 

This procarcinogen undergoes metabolic conversion to benzo[a]pyrene diol epoxides, BPDEs (5,28-31), which have been the focus of structural and conformational studies by theoretical and experimental methods. These chemically reactive BPDEs are involved in covalent binding to DNA (13-22). 

A theoretical analysis is presented for the binding of the four dia-stereoisomers of benzo[a]pyrene diol epoxides (BPDEs) to N2(g), N6(a), 06(G) and NU(c). Molecular models for binding and stereoselectivity involving intercalation, intercalative covalently and externally bound forms are presented. Molecular mechanics calculations provide the energetics which suggest possible structures for the formation of each of the principal DNA-BPDE complexes. Stereographic projections are used to illustrate the molecular structures and steric fits. The results of previous calculations on intercalation and adduct formation of BPDE l(+) in kinked DNA (37) are summarized and extended to include the four diastereoisomers l( ) and II( ). The theoretical model is consistent with the observed experimental data. 

J. W. Keller, C. Heidelberger, F. A. Beland, R. G. Harvey, Hydrolysis of syn- and anti-Benzo[a]pyrene Diol Epoxides Stereochemistry, Kinetics, and the Effect of an Intramolecular Hydrogen Bond on the Rate of. vyn-Diol Epoxide Solvolysis ,./. Am. Chem. Soc. 1976, 98, 8276 - 8277. 

Feldman, G., Remsen, J., Wang, TV., and Cerutti, P. (1980). Formation and excision of covalent deoxyribonucleic acid adducts of benzo[a]pyrene, 4,5-epoxide and benzo[a]pyrene diol epoxide I in human lung cells A549, Biochem. 19,1095. 

Harris, C.C., Vahakangas, K., Newman, M.J., Trivers, G.E., Shamsud-DIN, A., SiNOPOLi, N., Mann, D.L., and Wright, WE. (1985). Detection of benzo[a]pyrene diol epoxide-DNA adducts in peripheral blood lymphocytes and antibodies to the adducts in serum from coke oven workers, Proc. Natl. Acad. Sci. 82,6672. 

Electrophiles can be hard or soft. Thus hard electrophiles react with nucleophilic sites in molecules such as O, N, C in nucleic acids or the S in methionine in proteins. Hard electrophiles are typically genotoxic such as the benzo(a)pyrene diol epoxide (see chap. 7). 

Polycyclic aromatic hydrocarbons (PAH), which are ubiquitous in the environment, including surface waters, undergo facile chlorination by hypochlorite when dissolved in humus-poor water to give a suite of chlorinated PAH (1660). It is therefore conceivable that this chlorination can occur under natural conditions, but this is yet to be determined. Another new possible source of natural chlorinated PAH is the reported in vitro reaction of benzo [a pyrene diol epoxide, the ultimate carcinogen of benzo aIpyrene with chloride ion to give chlorohydrin DDD, which has been isolated and identified as an intermediate en route to a benzol a pyrene-DN A adduct (1661). However, DDD is not considered to be a natural compound at this time. 

Meehan T, Wolfe AR, Negrete GR, Song Q (1997) Benzo[a]pyrene Diol Epoxide-DNA cis Adduct Formation Through a trans Chlorohydrin Intermediate. Proc Natl Acad Sci USA 94 1749... 

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. 

Kasai, and K. Nakanishi. Benzo(a)pyrene diol epoxides as intermediates in nucleic acid binding in vitro and in vivo. Science 193 592-595, 1976. 

Manchester DK, Weston A, Choi JS, Trivers GE, Fennessey PV, Quintana E, Farmer PB, Mann DL, Harris CC (1988) Detection of benzo[a]pyrene diol epoxide-DNA adducts in human placenta. Proc Natl Acad Sci USA, 85(23) 9243-9247. 

Lodovici, M., Akpan, V., Giovannini, L., MigUani, F. Dolara, P. (1998). Benzo[n]pyrene diol-epoxide DNA adducts and levels of polycyclic aromatic hydrocarbons in autoptic samples from human lungs. Chemico-Biological Interactions, 116, 199-212. 

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