OXIDATIVE DAMAGE TO DNA DURING AGING - 8-HYDROXY-2'-DEOXYGUANOSINE IN RAT ORGAN DNA AND URINE
OXIDATIVE DAMAGE TO DNA DURING AGING - 8-HYDROXY-2'-DEOXYGUANOSINE IN RAT ORGAN DNA AND URINE
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DOI：
10.1073/pnas.87.12.4533
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发表时间：
1990-06-01
影响因子：
11.1
通讯作者：
AMES, BN
中科院分区：
文献类型：
--
作者：
FRAGA, CG;SHIGENAGA, MK;AMES, BN
对DNA的氧化损伤被证明是广泛的，并且可能是与衰老相关的生理变化和与衰老相关的退行性疾病（如癌症）的主要原因。氧化的核苷，8-羟基-2 "-脱氧鸟苷（oh8dG），其是其中一种。20种已知的氧化性DNA损伤产物，已经在从不同年龄的Fischer 344大鼠的各种器官分离的DNA中进行了测量。oh8dG存在于从所研究的所有器官分离的DNA中：肝、脑、肾、肠和睾丸。oh8dG的稳态水平为每106个脱氧鸟苷残基8 - 73个残基或0.2 - 2.0 × 106个脱氧鸟苷残基。每个细胞105个残基。DNA中的oh8dG水平随着年龄的增长而增加，在肝脏，肾脏和肠道，但在大脑和睾丸保持不变。尿中排泄的oh8dG，这大概反映了它的修复从DNA的核酸酶活性，随着年龄的增长，从481至165 pmol每公斤体重每天从2个月和25个月大的大鼠，分别获得的尿液。还测定了尿液中的8-羟基鸟嘌呤（糖基化酶活性的拟定修复产物）。我们估计.apprxeq。9倍。在大鼠中，每个细胞每天对DNA的氧化命中为104次。结果表明，从肝脏，肾脏和肠道的DNA中观察到的oh8dG残基的年龄依赖性积累主要是由于DNA核酸酶活性的缓慢丧失，但是，不能排除氧化性DNA损伤的速率增加。
Oxidative damage to DNA is shown to be extensive and could be a major cause of the physiological changes associated with aging and the degenerative diseases related to aging such as cancer. The oxidized nucleoside, 8-hydroxy-2''-deoxyguanosine (oh8dG), one of the .apprxeq. 20 known oxidative DNA damage products, has been measured in DNA isolated from various organs of Fischer 344 rats of different ages. oh8dG was present in the DNA isolated from all the organs studied: liver, brain, kidney, intestine, and testes. Steady-state levels of oh8dG ranged from 8 to 73 residues per 106 deoxyguanosine residues or 0.2-2.0 .times. 105 residues per cell. Levels of oh8dG in DNA increased with age in liver, kidney, and intestine but remained unchanged in brain and testes. The urinary excretion of oh8dG, which presumably reflects its repair from DNA by nuclease activity, decreased with age from 481 to 165 pmol per kg of body weight per day for urine obtained from 2-month-and 25-month-old rats, respectively. 8-Hydroxyguanine, the proposed repair product of a glycosylase activity, was also assayed in the urine. We estimate .apprxeq. 9 .times. 104 oxidative hits to DNA per cell per day in the rat. The results suggest that the age-dependent accumulation of oh8dG residues observed in DNA from liver, kidney, and intestine is principally due to the slow loss of DNA nuclease activity; however, an increase in the rate of oxidative DNA damage cannot be ruled out.