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      Evidence for N-(deoxyguanosin-8-yl)-1-aminopyrene as a major DNA adduct in female rats treated with 1-nitropyrene.

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          Abstract

          [3H]1-Nitropyrene was administered at a dose of 25 mg/kg by i.p. injection to female Wistar rats. Animals were killed 24 h later and DNA was isolated from kidney, liver and mammary gland, enzymically hydrolysed and analysed by reverse-phase h.p.l.c. A major adduct peak was detected in DNA from each of the three organs. Enzymic hydrolysates of DNA, which had been reacted in vitro with 1-nitropyrene in the presence of xanthine oxidase, were similarly analysed by h.p.l.c. One major adduct peak was obtained which had the same retention time as the in vivo product. Confirmatory evidence that the in vivo adduct and the in vitro adduct were structurally similar was obtained from the determination of the pH-dependent solvent partitioning profiles. Further, treatment of the in vivo adduct from liver, kidney or mammary gland DNA hydrolysates and the in vitro adduct with sodium hydroxide resulted in the formation of a more polar product which eluted earlier on h.p.l.c. This behaviour is consistent with scission of the imidazole ring of a deoxyguanosine adduct. The major DNA adduct formed in vitro following xanthine oxidase reduction of 1-nitropyrene has previously been identified by others as N-(deoxyguanosin-8-yl)-1-aminopyrene. The present data suggest that the in vivo 1-nitropyrene-DNA adduct has the same structure.

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          Author and article information

          Journal
          Carcinogenesis
          Carcinogenesis
          Oxford University Press (OUP)
          0143-3334
          0143-3334
          Apr 1985
          : 6
          : 4
          Article
          10.1093/carcin/6.4.535
          3838706
          ec131671-5fdb-4532-afdf-0b42d909de6d
          History

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