Adelman R, Saul R L, Ames B N
Department of Biochemistry, University of California, Berkeley 94720.
Proc Natl Acad Sci U S A. 1988 Apr;85(8):2706-8. doi: 10.1073/pnas.85.8.2706.
Oxidative damage to DNA is caused by reactive by-products of normal metabolism, as well as by radiation. Oxidized DNA bases excised by DNA repair enzymes and excreted in urine were measured in four different species to determine the relation between specific metabolic rate (ml of O2 consumed per gram of body weight per hr) and oxidative DNA damage. An average of 6.04 nmol of thymine glycol per kg/day and 2.58 nmol of thymidine glycol per kg/day were found in mouse urine and 1.12 nmol of thymine glycol per kg/day and 0.95 nmol of thymidine glycol per kg/day were found in monkey urine. On a body weight basis, mice excrete 18 times more thymine glycol plus thymidine glycol than do humans, and monkeys excrete 4 times more thymine glycol plus thymidine glycol than do humans. When results among mice, rats, monkeys, and humans are compared, specific metabolic rate correlates highly with oxidative DNA damage. These findings are consistent with the theory that free radical-induced DNA damage may play a central role in the aging process.
DNA的氧化损伤是由正常新陈代谢的活性副产物以及辐射引起的。通过测量四种不同物种中被DNA修复酶切除并随尿液排出的氧化DNA碱基,来确定特定代谢率(每克体重每小时消耗的氧气毫升数)与氧化DNA损伤之间的关系。在小鼠尿液中平均发现每千克每天6.04纳摩尔的胸腺嘧啶乙二醇和2.58纳摩尔的胸苷乙二醇,在猴子尿液中发现每千克每天1.12纳摩尔的胸腺嘧啶乙二醇和0.95纳摩尔的胸苷乙二醇。以体重为基础,小鼠排出的胸腺嘧啶乙二醇加胸苷乙二醇比人类多18倍,猴子排出的胸腺嘧啶乙二醇加胸苷乙二醇比人类多4倍。当比较小鼠、大鼠、猴子和人类的结果时,特定代谢率与氧化DNA损伤高度相关。这些发现与自由基诱导的DNA损伤可能在衰老过程中起核心作用的理论一致。