IDENTIFICATION OF N(2)-(DEOXYGUANOSIN-8-YL)-2-AMINO-3,8-DIMETHYLIMIDAZO[4,5-F]QUINOXALINE 3',5'-DIPHOSPHATE, A MAJOR DNA ADDUCT, DETECTED BY NUCLEASE P1 MODIFICATION OF THE P-32 POSTLABELING METHOD, IN THE LIVER OF RATS FED MEIQX

被引：40

作者：

OCHIAI, M ^{[1
]}

NAGAOKA, H ^{[1
]}

WAKABAYASHI, K ^{[1
]}

TANAKA, Y ^{[1
]}

KIM, SB ^{[1
]}

TADA, A ^{[1
]}

NUKAYA, H ^{[1
]}

SUGIMURA, T ^{[1
]}

NAGAO, M ^{[1
]}

机构：

[1] UNIV SHIZUOKA,SCH PHARMACEUT SCI,SHIZUOKA 422,JAPAN

来源：

CARCINOGENESIS | 1993年 / 14卷 / 10期

关键词：

D O I：

10.1093/carcin/14.10.2165

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 P-32-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 [C-14]MeIQx intragastrically. By the nuclease PI method rive 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 P-32-postlabeling method in combination with HPLC, and thus provide information on the roles of MeIQx in human carcinogenesis.

引用

页码：2165 / 2170

页数：6

共 31 条

[1] MUTAGENIC ACTIVATION OF IQ, PHIP AND MEIQX BY HEPATIC MICROSOMES FROM RAT, MONKEY AND MAN - LOW MUTAGENIC ACTIVATION OF MEIQX IN CYNOMOLGUS MONKEYS INVITRO REFLECTS LOW DNA ADDUCT LEVELS INVIVO [J].