RELEASE OF N2,3-ETHENOGUANINE FROM CHLOROACETALDEHYDE-TREATED DNA BY ESCHERICHIA-COLI 3-METHYLADENINE DNA GLYCOSYLASE-II

被引:82
作者
MATIJASEVIC, Z
SEKIGUCHI, M
LUDLUM, DB
机构
[1] UNIV MASSACHUSETTS,SCH MED,DEPT PHARMACOL,WORCESTER,MA 01655
[2] KYUSHU UNIV 60,FAC MED,DEPT BIOCHEM,FUKUOKA 812,JAPAN
关键词
ENVIRONMENTAL CARCINOGENESIS; MUTAGENESIS; DNA MODIFICATION; DNA REPAIR; CYCLIC DNA ADDUCTS;
D O I
10.1073/pnas.89.19.9331
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The human carcinogen vinyl chloride is metabolized in the liver to reactive intermediates which form N2,3-ethenoguanine in DNA. N2,3-Ethenoguanine is known to cause G --> A transitions during DNA replication in Escherichia coli, and its formation may be a carcinogenic event in higher organisms. To investigate the repair of N2,3 -ethenoguanine, we have prepared an N2,3-etheno[C-14]guanine-containing DNA substrate by nick-translating DNA with [C-14]dGTP and modifying the product with chloroacetaldehyde. E. coli 3-methyladenine DNA glycosylase II, purified from cells which carry the plasmid pYN1000, releases N2,3-ethenoguanine from chloroacetaldehyde-modified DNA in a protein- and time-dependent manner. This finding widens the known substrate specificity of glycosylase II to include a modified base which may be associated with the carcinogenic process. Similar enzymatic activity in eukaryotic cells might protect them from exposure to metabolites of vinyl chloride.
引用
收藏
页码:9331 / 9334
页数:4
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