Analysis of an RNA adduct formed from aminophenylnorharman.

Koichi Nishimura, Yukari Totsuka, Takashi Higuchi, Nobuo Kawahara, Takashi Sugimura, Keiji Wakabayashi
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引用次数: 2

Abstract

The endogenous mutagenic/carcinogenic 9- (4'-aminophenyl) -9H- pyrido [3,4-b] indole (aminophenylnorharman, APNH) is formed from norharman and aniline in the presence of cytochrome P-450s. The major APNH-DNA adduct has been reported to be 2'-deoxyguanosin-8-yl-aminophenylnorhaman (dG-C8-APNH). In addition, demonstrated formation of APNH-RNA adduct and conducted a structural analysis using various spectrometric approaches. The compound produced from guanosine (Guo) and N-acetoxy-APNH, an ultimate mutagenic form of APNH, was concluded to be guanosin-8-yl-APNH (Guo-C8-APNH) on the basis of various spectroscopic analysis. The same adduct was found in the livers of rats administered APNH. The total adduct levels of APNH-RNA were six times higher than total APNH-DNA adducts in the same rat liver samples.

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氨基苯基诺哈曼形成的RNA加合物的分析。
内源性致突变/致癌物质9-(4′-氨基苯基)- 9h -吡啶[3,4-b]吲哚(aminophenylnorharman, APNH)是由norharman和苯胺在细胞色素p -450存在下形成的。据报道,APNH-DNA的主要加合物是2'-脱氧鸟苷-8-基氨基苯基诺哈曼(dG-C8-APNH)。此外,证明了APNH-RNA加合物的形成,并使用各种光谱方法进行了结构分析。鸟苷(Guo)与n-乙酰氧基-APNH (APNH的最终致突变性形式)合成的化合物经多种光谱分析确定为鸟苷-8-yl-APNH (Guo- c8 -APNH)。在给予APNH的大鼠肝脏中也发现了相同的加合物。在相同的大鼠肝脏样本中,APNH-RNA的总加合物水平比APNH-DNA的总加合物高6倍。
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