| 7273322 |
Meerman JH, Beland FA, Mulder GJ: Role of sulfation in the formation of DNA adducts from N-hydroxy-2-acetylaminofluorene in rat liver in vivo. Carcinogenesis. 1981;2(5):413-6.
Inhibition of N-acetylated aminofluorene adduct formation by pentachlorophenol.. N-Hydroxy-2-acetylaminofluorene (N-OH-AAf) is metabolically converted into reactive N,O-esters which are capable of forming covalent adducts with DNA in rat liver in vivo. The effect of inhibiting one of the proposed pathways, N-O-sulfation, on DNA adduct formation was studied by using a specific sulfotransferase inhibitor, pentachlorophenol. Rats were pretreated with pentachlorophenol and, after 45 min, N-OH-AAF was administered. Four hours after dosing the animals were sacrificed and hepatic DNA was isolated. In DNA from control livers two acetylaminofluorene-and one aminofluorene-substituted deoxyguanosine adducts were found. The acetylaminofluorene derivatives, N-(deoxyguanosin-8-yl)-2--acetylaminofluorene and 3-(deoxyguanosin-N2-yl)-2acetylaminofluorene, accounted for 40% of the total binding in the hydrolyzed DNA. The aminofluorene adduct, N-(deoxyguanosin-8-yl)-2-aminofluorene, accounted for the remainder. In rats that were pretreated with pentacholorphenol, total DNA binding was decreased by 26%. The same three adducts were found, but the acetylaminofluorene adducts were now only 13% of the total, while the aminofluorene adduct accounted for 87%. The absolute amount of aminofluorene adduct was not altered as compared to control rats. These data demonstrate the involvement of N-O-sulfation in carcinogen-DNA binding and indicate that at least 70% of the acetylaminofluorene bound to deoxyguanosine in rat liver DNA, in vivo, is formed through N-O-sulfation of N-OH-AAF. |
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