Background levels of DNA damage in the population.
Background levels of DNA damage in the population.
复制标题
人群中 DNA 损伤的背景水平。
DOI：
10.1007/978-1-4615-9462-8_55
复制
发表时间：
1986
期刊：
影响因子：
--
通讯作者：
Ames,BN
中科院分区：
文献类型：
--
作者：
Saul,RL;Ames,BN
除了人造诱变物质的危险之外，还有各种自然产生的物质和过程可以对人体造成DNA损伤。这些因素包括外源性因素，如阳光和饮食诱变剂，以及内源性因素，如通过正常代谢在细胞内形成的活性氧。这些过程可导致至少六种主要类型的DNA损伤：碱基丢失、碱基脱氨、碱基烷基化、碱基二聚化、碱基氧化和单链断裂。基于无细胞模型系统或培养细胞的钙蛋白体外测量，对这些病变的产生率进行了估计：每天约有26,000个碱基损失，主要是嘌呤损失，因为糖基键的自发水解；每天约有350个胞嘧啶分解；每天有数以万计的碱基烷基化，主要是由s -腺苷蛋氨酸引起的鸟嘌呤甲基化；每天多达50,000个嘧啶二聚体，取决于暴露在阳光下；每天大约有10万条单链断裂。根据对人体尿液中DNA氧化产物的测量，我们估计，人体中所有氧化DNA损伤产物的总形成率在每个细胞每天几千个事件的顺序上。此外，由于互变异构移位、碱基电离或碱基旋转，碱基错配可以在没有DNA损伤的情况下发生。这种对DNA损伤形成的估计只是非常近似的，因为它们是基于有限的数据，而且在大多数情况下，由于三级和四级DNA结构以及组蛋白、二价阳离子和体内其他因素的存在，许多可能的影响都没有得到纠正。每个特定病变的生物学重要性很难获得，因为这不仅取决于形成的速度，而且取决于该病变在DNA中的持久性和化学性质。大多数病变的稳态浓度可能在体内非常低，因为各种有效的DNA修复酶可以修复损伤，“校对”酶可以纠正碱基不匹配。虽然这种损害背景的重要性很难评估。通过与这一背景进行比较，有可能评估环境诱变剂的相对重要性。
In addition to the dangers of man-made mutagenic substances, there exist a variety of naturally-occurring agents and processes than can cause DNA damage in man. These include exogenous agents, such as sunlight and dietary mutagens, as well as endogenous agents, such as reactive oxygen species which are formed within the cell via normal metabolism. These processes can lead to at least six major types of DNA damage: base loss, base deamination, base alkylation, base dimerization, base oxidation, and single-strand breakage. Based uponin vitromeasurements in cell-free model systems or cultured cells, estimates of the rates of production of these lesions have been made for the average human cell: about 26,000 base losses per day, primarily purines lost because of spontaneous hydrolysis of the glycosyl bond; about 350 cytosine deaminations per day; tens of thousands of base alkylations per day, primarily methylations of guanine caused by S-adenosylmethionine; up to 50,000 pyrimidine dimerizations per day, dependent upon exposure to sunlight; and about 100,000 single-strand breaks per day. Based upon measurements of DNA oxidation products in human urine, we estimate that the total rate of formation of all oxidative DNA damage products in man is on the order of a few thousand events per cell per day. In addition, base mispairing can take place in the absence of DNA damage because of tautomeric shifts, base ionization, or base rotation. Such estimates of DNA lesion formation are only very approximate because they are based on limited data, and in most cases have not been corrected for the many possible influences of tertiary and quaternary DNA structure and the presence of histones, divalent cations, and other factorsin vivo. The biological importance of each particular lesion is difficult to access since this depends not only on the rate of formation, but also on the persistence and chemical nature of that lesion within the DNA. The steady-state concentrations of most lesions are probably very lowin vivobecause of a variety of efficient DNA repair enzymes that repair damage, and “proof-reading” enzymes that correct base mismatching. Although the importance of this background of damage is difficult to evaluateper se. it may be possible to assess the relative importance of environmental mutagens by comparison to this background.
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影响因子：
56.9
作者：
AMES, BN
通讯作者：
AMES, BN
S-腺苷甲硫氨酸和S-腺苷高半胱氨酸在大鼠体内的组织分布。
影响因子：
4.1
作者：
T. Eloranta
通讯作者：
T. Eloranta
自发性癌症及其与氧代谢的可能关系。
DOI：
--
发表时间：
1980
影响因子：
11.1
作者：
J. Totter
通讯作者：
J. Totter
衰老的分子生物学：基因稳定性和基因表达
DOI：
--
发表时间：
1985
期刊：
影响因子：
--
作者：
R. S. Sohal;L. Birnbaum;R. Cutler
通讯作者：
R. Cutler
影响因子：
2.9
作者：
LINDAHL, T;ANDERSSON, A
通讯作者：
ANDERSSON, A