DNA Adducts Formed from p-Benzoquinone, an Electrophilic Metabolite of Benzene, Are Extensively Metabolized in Vivo

Benzetheno adducts derived from p-benzoquinone (p-BQ), a reactive metabolite of benzene, were reported to be formed by the reaction of p-BQ with DNA in vitro but have never been detected either in vivo or in experiments with living cells. Two of them, 3-hydroxy-3,N4-benzetheno-2′-deoxycytidine (DCBQ) and 7-hydroxy-1,N2-benzetheno-2′-deoxyguanosine (DGBQ), were administered to rats by single ip injections at the doses of 2 mg/kg each. The excretion of unchanged compounds DCBQ and DGBQ within 2 days amounted to 8.2 ± 1.9 and 4.5 ± 1.2% (mean ± SE) of the dose, respectively. Additionally, deribosylated metabolites of DCBQ and DGBQ, 3-hydroxy-3,N4-benzethenocytosine (CBQ) and 7-hydroxy-1,N2-benzethenoguanine (GBQ), were found amounting to 45.7 ± 10.2 and 2.9 ± 2.1% of the dose, respectively. An additional portion of CBQ and GBQ was liberated from their corresponding conjugates by acidic hydrolysis. Therefore, total recoveries of CBQ and GBQ in urine were 82.1 ± 13.5 and 11.6 ± 5.1% of the dose. To identify co...