Benzene expresses its carcinogenic potential in humans largely in the form of acute
leukemia. Because an understanding of the formation of
DNA adducts by
benzene metabolites may help to explain the etiological role they play in
benzene-induced
bone marrow disease, we have synthesized, isolated and characterized adducts formed by the reaction of
deoxyguanosine with
hydroquinone and
p-benzoquinone, two toxic metabolites of
benzene. [3H]
Deoxyguanosine and [14C]
hydroquinone reacted in neutral aqueous
buffer containing
iron to form two dual-labeled products, which were separated using HPLC. When
p-benzoquinone was substituted for
hydroquinone, the same adducts were formed in the absence of added
iron. The ultraviolet and fluorescence spectra of the less polar adduct, called Adduct 2, were distinctly different from the spectra of the starting materials. NMR and mass spectrometry suggested a compound with a mass of 357 with the
p-benzoquinone moiety bound to the N-1 and N2 positions of
deoxyguanosine. Based on these data it is proposed that Adduct 2 is (3'
OH)benzetheno(1,N2)
deoxyguanosine. The more polar product, Adduct 1, was found to have a unique ultraviolet spectrum but did not appear to be fluorescent. Both adducts were observed after
calf thymus DNA was incubated with
hydroquinone and digested to its constituent
nucleosides.