Diol Epoxide-DNA Adducts

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. 

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. 

Haugen A. Becher G, Benestad C, et al. 1986. Determination of polycyclic aromatic hydrocarbons in the urine. benzo(a)pyrene diol epoxide-DNA adducts in lymphocyte DNA, and antibodies to the adducts in sera from coke oven workers exposed to measured amount of polycyclic aromatic hydrocarbons in the work atmosphere. Cancer Res 46 4178-4183. 

Newman MJ, Light BA, Weston A, et al. 1988. Detection and characterization of human serum antibodies to polycyclic aromatic hydrocarbon diol-epoxide DNA adducts. J Clin Invest (United States) 82 145-153. 

PAH diol epoxide-DNA adducts have not only been detected in rodent tissues in experimental systems after PAH exposure, but have also been identified in (a) populations exposed to complex mixtures containing PAHs, (b) foundry workers (Perera et al. 1988 Hemminki et al. 1988), (c) coke oven workers (Rojas et al. 1995 Pavanello et al. 1999), (d) cigarette smokers (Lodovici et al. 1998 Rojas et al. 1995), (e) chimney sweeps (Pavanello et al. 1999), and (f) populations exposed to smoky coal combustion mixtures (Mumford et al. 1993). Some bay- or fjord-region diol epoxides form DNA adducts in the human p53 tumor suppressor gene at sites that are hotspots for lung cancer (Smith et al. 2000). 

Ruan, Q., Kim, H. Y, Jiang, H., Penning, T. M., Harvey, R. G., and Blair, I. A. (2006). Quantification of benzo[a]pyrene diol epoxide DNA-adducts by stable isotope dilution liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 20, 1369—1380. 

Rojas M, Godschalk R, Alexandrov K, et al. 2001. Myeloperoxidase—463A varient reduces benzo[alpha]pyrene diol epoxide DNA adducts in skin of coal tar treated patients. Carcinogenesis 22(7) 1015-1018. 

Scheme 6.5 Diol epoxide-DNA adducts - different stereochemistries.

Figure 12.2 Chemical structures of the PAH compounds considered in this chapter, definitions of the bay and fjord region topologies, the stereochemical characteristics of the biologically relevant PAH diol epoxide metabolites, and stereochemical characteristics of PAH diol epoxide-DNA adducts. The aromatic rings metabolized by mammalian CYP 450 enzymes are the 7,8,9,10 ring of B[o]P, the 1,2,3,4 ring of B[c]Ph, and the 11,12,13,14 rings of B[g]C and DB[o,/]P. The absolute configurations of the PAH diol epoxides and DNA adducts are illustrated in the case of the (+)- and (-)-arrt/-B[a]PDE diol...

In order to delineate the structural and dynamic properties of PAH diol epoxide-DNA adducts and their correlations to DNA repair susceptibility, a powerful array of complementary methods have been employed (e.g., [78]) ... 

In order to compare the relative NER efficiencies of our PAH diol epoxide-DNA adducts we prepared site-specifically modified oligonucleotides containing either CPD or 6-4 photodimers using the same sequence and methods as described in the literature [110], Typical results obtained in our laboratory are displayed in Figure 12.6(a). There are fewer NER dual-incision bands in the case of the CPD dimer than in the case of the 6-4 photoproduct and the latter are clearly more intense than the former. Densitometry analysis shows that the time course of dual incisions is linear at least up to 40 min and that the DNA strand bearing the 6-4 adduct is around 17 times faster than the strand with the CPD dimer (Figure 12.6c). The repair rate of the (+)-cis-anti-B[a] P-N2-dG adduct and the 6-4 photoproduct coincide with one another (Figure 12.6c), as described in more detail elsewhere [78],... 

Hanrahan, C.J., Bacolod, M.D., Vyas, R.R., Liu, T., Geacintov, N.E., Loechler, E.L., and Basu, A.K. (1997) Sequence specific mutagenesis of the major (+)- nti-benzo[a]pyrene diol epoxide-DNA adduct at a mutational hot spot in vitro and in Escherichia coli cells. Chem. Res. Toxicol, 10, 369-377. 

Use of UvrABC nuclease to quantify benzojajpyrene diol epoxide-DNA adduct formation at methylated versus unmethylated CpG sites in the p53 gene. Carcinogenesis, 20, 1085-1089. 

Choi, D.J., Marino-Alessandri, D.J., Geacintov, N.E., and Scicchitano, D.A. (1994) Site-specific benzo[a]pyrene diol epoxide-DNA adducts inhibit transcription elongation by bacteriophage T7 RNA polymerase. Biochemistry, 33, 780-787. 

Weston, A. Newman, M. J. Mann, D. L. Brooks, B. R. Molecular mechanics and antibody binding in the structural analysis of polycyclic aromatic hydrocarbon diol-epoxide DNA adducts. Carcinogenesis (Lond), 11 859-64. 1990. 

For benzo[fl]pyrene diol-epoxide-DNA adducts in leucocytes of coke-oven workers exposed to polycychc aromatic hydrocarbons, a sensitive, specific high-performance liquid chromatography-fluorescence assay was developed and validitated to monitor the levels of (+)-a ti-benzo[a]pyrene diol-epoxide bound to DNA by the release of the respective benzo[fl]pyrene-tetrols from tissue or leucocyte DNA (Alexandrov et al. 1992). 

Zenzes MT, Puy LA, Bielecki R, Reed TE Detection of benzo[a]pyrene diol epoxide-DNA adducts in embryos from smoking couples evidence for transmission by spermatozoa. Mol Hum Reprod 1999, 5 125-131. 

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