Acetylaminofluorene deoxyguanosine adduct

Human exposures to chemicals found in certain foods or environmental pollutants are linked to a higher risk for cancer. It is known that the initial step in chemical carcinogenesis is the covalent attachment of the chemical to DNA to produce DNA adducts. The structure identification of these DNA adducts is very important in cancer research. CEC-ESI-MS with shealth liquid interface has been demonstrated as a good tool for the analysis of DNA adducts as well as nucleosides with styrene oxide by Vouros and co-authors [24, 25]. Two common DNA adducts, acetylaminofluorene deoxyguanosine (AAF-dG) and an isomer of anti-benzo[g]chrysene 11,12-dihydrodiol 13,14-epoxide, were employed as model compounds. CEC separation was performed on a Cig silica gel-packed column and used a mixture of 60% acetonitrile and 5 mM ammonium acetate as the mobile phase. Figure 10 shows the extracted ion electrochromatograms and mass spectra of AAF-dG and benzo[g]chrysene-dG [25]. 

Poirier, M.C., Williams, G.M. and Yuspa, S.H. (1980). Effect of culture conditions cell type and species of origin on the distribution of acetylated and deacetylated deoxyguanosine C-8 adducts of A-acetoxy-2-acetylaminofluorene. Mol. Pharmacol. 18 581-587. 

C. C. Lai, E. C. Miller, A. Liem, The Essential Role of Microsomal Deacetylase Activity in the Metabolic Activation, DNA-(Deoxyguanosin-8-yl)-2-aminofluorene Adduct Formation and Initiation of Liver Tumors by A-Hydroxy-2-acetylaminofluorene in the Livers of Infant Male B6C3Fj Mice , Carcinogenesis 1988, 9, 1295-1302. 

Fig. 8.25. CEC—ESI-MS analysis of the adducts between acetylaminofluorene or the dihydodiol epoxide of benzofgjchrysene with deoxyguanosine. Column, 280 x 0.075 mm i.d. packed with 5 pm/100 A Nucleosil-C18 eluent, 5 mmol/1 ammonium acetate, 60% acetonitrile applied voltage, 125 kV detection, ESI-MS, 370-470 amu sheath liquid, 2 mmol/1 aqueous ammonium acetate, 50% acetonitrile, 3 pl/min injection, electrokinetic, 12 kV, 7 min. (Reprinted with permission from ref. [100]. Copyright [1997] American Chemical Society.).

Fig. 8.26. Mass spectra of the adducts between (a) acetylaminofluorene or the (b) dihydodiol epoxide of benzo[g]chrysene with deoxyguanosine. (Reprinted with permission from ref. [100]. Copyright [1997] American Chemical Society).

Zaliznyak, T., Bonala, R., Johnson, F., and de los Santos, C. (2006) Structure and stability of duplex DNA containing the 3-(deoxyguanosin-JV2-yl)-2-acetylaminofluorene (dG(N2)-AAF) lesion a bulky adduct that persists in cellular DNA. Chem. Res. Toxicol., 19, 745-752. 

Yasui, M., Dong, H., Bonala, R.R., Suzuki, N., Ohmori, H., Hanaoka, F., Johnson, F., Grollman, A.P., and Shibutani, S. (2004) Mutagenic properties of 3-(deoxyguanosin-N2-yl)-2-acetylaminofluorene, a persistent acetylaminofluorene-derived DNA adduct in mammalian cells. Biochemistry, 43,15005-15013. 

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