Characterization of a deoxyguanosine adduct of tetrachlorobenzoquinone: dichlorobenzoquinone-1,N2-etheno-2'-deoxyguanosine.
Pentachlorophenol (PCP), a widespread environmental pollutant that is possibly carcinogenic to humans, is metabolically oxidized to tetrachloroquinone. DNA adducts attributable to tetrachloroquinone have been observed previously in vitro and detected in vivo. In addition, an unidentified adduct in these studies coeluted with the product of the reaction of deoxyguanosine (dG) and tetrachlorobenzoquinone (Cl4BQ). We have synthesized, isolated, purified, and characterized the predominant adduct formed from the reaction of dG and Cl4BQ. The preparation of a 13C-labeled version of this adduct facilitated its structural characterization. On the basis of 1H NMR, 13C NMR, MS, IR, UV, and cyclic voltammetry, we propose that the adduct is a dichlorobenzoquinone nucleoside in which two chlorine atoms in Cl4BQ have been displaced by reaction at the 1- and N2-positions of dG. The 1H and 13C NMR chemical shifts are consistent with the dichlorobenzoquinone assignment. In contrast, under standard analytical conditions, LC-MS data are consistent with a reduced hydroquinone structure, similar to what may be expected based on results from other chloroquinones. Data from the present study indicate that this reduction could be occurring in the electrospray ionization source and that the initial product of the reaction of dG and Cl4BQ is a dichlorobenzoquinone. The results of this study contribute to the hypothesis that direct reactions between chlorophenols and DNA may play a role in the toxic effects of chlorophenols and indicate a potential difference in reactivity and biological influence between PCP and other less substituted chlorophenols or phenols.
Nguyen
Thu N T
TN
Department of Medicinal Chemistry, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Bertagnolli
Anthony D
AD
Villalta
Peter W
PW
Bühlmann
Philippe
P
Sturla
Shana J
SJ
D001711:Biotransformation; D002703:Chloranil / Q000378:metabolism*; D018736:DNA Adducts / Q000737:chemistry*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D010416:Pentachlorophenol / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization
D018736:DNA Adducts; D002703:Chloranil; D010416:Pentachlorophenol; D003849:Deoxyguanosine