DNA METHYLATION BY TERT-BUTYL HYDROPEROXIDE-IRON(II)

被引:49
作者
HIX, S [1 ]
MORAIS, MD [1 ]
AUGUSTO, O [1 ]
机构
[1] UNIV SAO PAULO, INST CHEM, DEPT BIOCHEM, BR-05599970 SAO PAULO, BRAZIL
基金
巴西圣保罗研究基金会;
关键词
TERT-BUTYL HYDROPEROXIDE; HYDROPEROXIDES; FREE RADICALS; IRON; SPIN-TRAPPING; DNA METHYLATION; DNA ALKYLATION; DNA-ADDUCTS; C-8-METHYLGUANINE; N-7-METHYLGUANINE;
D O I
10.1016/0891-5849(95)00026-T
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Reduction of tert-butyl hydroperoxide (TBHP) by iron (II) at pH 4.0 or pH 7.0 in the presence of calf thymus DNA led to generation of high yields of methyl radicals and to DNA methylation. Methyl radicals were identified by spin-trapping experiments with 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN). The methylated DNA-base adducts were identified in treated DNA hydrolysates by high pressure liquid chromatography (HPLC) and photodiode array UV spectroscopy. In the case of DNA several methylated adducts were identified, namely N-7-methylguanine, C-8-methylguanine, N-3-methyladenine, and O-6-methylguanine. By contrast, 2'-deoxyguanosine is alkylated almost exclusively to C-8-methyl-2'-deoxyguanosine. These results constitute the first evidence that TBHP is able to alkylate DNA.
引用
收藏
页码:293 / 301
页数:9
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