Identification of N2-(deoxyguanosin-8-yl)-2-amino-3,8-dimethyl-imidazo[4,5- f]quinoxaline 3',5'-diphosphate, a major DNA adduct, detected by nuclease P1 modification of the 32P-postlabeling method, in the liver of rats fed MeIQx.
Identification of N2-(deoxyguanosin-8-yl)-2-amino-3,8-dimethyl-imidazo[4,5- f]quinoxaline 3',5'-diphosphate, a major DNA adduct, detected by nuclease P1 modification of the 32P-postlabeling method, in the liver of rats fed MeIQx.
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N2-(脱氧鸟苷-8-基)-2-氨基-3,8-二甲基-咪唑并[4,5-f]喹喔啉3,5-二磷酸的鉴定，这是一种主要的DNA加合物，通过核酸酶P1修饰检测
DOI：
10.1093/carcin/14.10.2165
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发表时间：
1993
期刊：
影响因子：
4.7
通讯作者：
M. Nagao
中科院分区：
文献类型：
--
作者：
M. Ochiai;H. Nagaoka;K. Wakabayashi;Y. Tanaka;S. B. Kim;A. Tada;H. Nukaya;T. Sugimura;M. Nagao
致癌的杂环胺2-氨基-3，8-二甲基-咪唑并[4，5-f]喹喔啉（MeIQx）广泛存在于熟食中。核酸酶P1方法提高了标准32 P-后标记分析的灵敏度约1000倍，用于检测MeIQx-DNA加合物。使用经[14 C]MeIQx灌胃处理的大鼠的肝脏DNA，通过核酸酶P1法测定MeIQx-DNA加合物的回收率约为50%。通过核酸酶P1方法，在喂食MeIQx的大鼠的肝脏DNA中检测到五种加合物，其中两种，包括最丰富的一种，通过与N-乙酰氧基-2-氨基-3，8-二甲基咪唑[4，5-f]喹喔啉与四种2 '-脱氧核糖核苷酸体外反应形成的加合物进行比较，鉴定为MeIQx-脱氧鸟苷加合物。体内最丰富的加合物被鉴定为N2-（脱氧鸟苷-8-基）-MeIQx 3 '，5'-二磷酸（3 '，5'-pdGp-C8-MeIQx）。MeIQx-DNA加合物在人体组织中的水平可以通过核酸酶P1修饰的32 P-后标记方法结合HPLC来确定，从而提供关于MeIQx在人类致癌作用中的作用的信息。
The carcinogenic heterocyclic amine 2-amino-3,8-dimethyl-imidazo[4,5-f]quinoxaline (MeIQx) is widely distributed in cooked foods. The nuclease P1 method increased the sensitivity of the standard 32P-postlabeling analysis about 1000-fold for detection of MeIQx-DNA adducts. The recovery of MeIQx-DNA adducts by the nuclease P1 method was determined to be about 50% using liver DNA of a rat treated with [14C]MeIQx intragastrically. By the nuclease P1 method five adducts were detected in the liver DNA of rats fed MeIQx and two of them, including the most abundant one, were identified as MeIQx-deoxyguanosine adducts by comparison with the adducts formed in in vitro reactions of N-acetoxy-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline with the four 2'-deoxyribonucleotides. The most abundant adduct in vivo was identified as N2-(deoxyguanosin-8-yl)-MeIQx 3',5'-diphosphate (3',5'-pdGp-C8-MeIQx). MeIQx-DNA adduct levels in human tissues could be determined by the nuclease P1 modification of the 32P-postlabeling method in combination with HPLC, and thus provide information on the roles of MeIQx in human carcinogenesis.