MASSIVE CONVERSION OF GUANOSINE TO 8-HYDROXY-GUANOSINE IN MOUSE-LIVER MITOCHONDRIAL-DNA BY ADMINISTRATION OF AZIDOTHYMIDINE

被引:105
作者
HAYAKAWA, M
OGAWA, T
SUGIYAMA, S
TANAKA, M
OZAWA, T
机构
[1] Department of Biomedical Chemistry, Faculty of Medicine, University of Nagoya, Nagoya
关键词
D O I
10.1016/0006-291X(91)90893-C
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
As typical mitochondrial myopathy has been reported to be expressed among many patients with AIDS treated with long-term azidothymidine (AZT) therapy, we examined changes in mouse liver mitochondrial DNA (mtDNA) after 4-week administration of AZT. Even below 1 10th the dose given to the patients (AZT, 1 mg/kg/day), 25% of the total deoxyguanosine (dG) was converted to be 8-hydroxy-deoxyguanosine (8-OH-dG). 38% of the total dG was converted to 8-OH-dG with AZT 5 mg/kg/day. In vitro, the conversion of dG to 8-OH-dG was demonstrated by incubating mtDNA in the oxygen radical producing system containing NADH and KCN treated mitochondrial inner membrane. Thus it is concluded that, by lack of repairing system, damaged mtDNA with AZT results in impaired mitochondrial respiratory chain causing oxygen radicals which are responsible for 8-OH-dG formation. These results suggest that the oxygen damage of mtDNA is the primary cause of mitochondrial myopathy with AZT therapy. © 1991.
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页码:87 / 93
页数:7
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