ASCORBIC-ACID PROTECTS AGAINST ENDOGENOUS OXIDATIVE DNA DAMAGE IN HUMAN SPERM
ASCORBIC-ACID PROTECTS AGAINST ENDOGENOUS OXIDATIVE DNA DAMAGE IN HUMAN SPERM
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DOI：
10.1073/pnas.88.24.11003
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发表时间：
1991-12-01
影响因子：
11.1
通讯作者：
AMES, BN
中科院分区：
文献类型：
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作者：
FRAGA, CG;MOTCHNIK, PA;AMES, BN
生殖细胞的DNA损伤可能导致突变，这可能导致出生缺陷、遗传病和癌症。DNA氧化损伤的内源性很高，以及饮食中抗坏血酸(AA)在预防这种损伤方面的重要性，促使人们对人类精子DNA中的这些因素进行了研究。用8-氧代-7，8-二氢-2‘-脱氧鸟苷(8-oxo-7，8-二氢-2’-脱氧鸟苷；oxo8dG)作为DNA氧化损伤的主要产物之一，测定了正常人精液DNA中的氧化核苷8-羟基-2‘-脱氧鸟苷(8-oxo-7，8-diwater-2’-deoxguanosine；oxo8dG)，并与精液中的AA水平进行了比较。这种关系在两组中进行了研究。在24名20-50岁的自由生活个体中，高水平的oxo8dG与低的精浆AA水平相关。这组人的内源性oxo8dG水平为每微克DNA 13fmoL，或几乎相当于每个精子细胞25,000个加合物。第二组受试者只吃AA含量不同的受控饮食。当日粮AA从250 mg/d降至5 mg/d时，精液AA减少一半，精子DNA中oxo8dG含量增加91%。补充日粮AA 28天(从5 mg/天增加到250或60 mg/天)，精液AA增加一倍，oxo8dG降低36%。这些结果表明，膳食AA保护人类精子免受内源性氧化DNA损伤，这种损伤可能会影响精子质量并增加遗传缺陷的风险，特别是在吸烟者等AA低的人群中。
Damage to the DNA of germ cells can lead to mutation, which may result in birth defects, genetic diseases, and cancer. The very high endogenous rate of oxidative DNA damage and the importance of dietary ascorbic acid (AA) in preventing this damage has prompted an examination of these factors in human sperm DNA. The oxidized nucleoside 8-hydroxy-2'-deoxyguanosine (8-oxo-7,8-dihydro-2'-deoxyguanosine; oxo8dG), 1 of almost-equal-to 20 major products of oxidative damage to DNA, was measured in DNA isolated from human sperm provided by healthy subjects and compared to the seminal fluid AA levels. This relationship was studied in two groups. In a group of 24 free-living individuals 20-50 years old high levels of oxo8dG were correlated with low seminal plasma AA. The endogenous level of oxo8dG in this group was 13 fmol per mu-g of DNA or almost-equal-to 25,000 adducts per sperm cell. The second group of individuals was maintained on a controlled diet that varied only in AA content. When dietary AA was decreased from 250 to 5 mg/day, the seminal fluid AA decreased by half and the level of oxo8dG in sperm DNA increased 91%. Repletion of dietary AA for 28 days (from 5 mg/day to 250 or 60 mg/day) caused a doubling in seminal fluid AA and reduced oxo8dG by 36%. These results indicate that dietary AA protects human sperm from endogenous oxidative DNA damage that could affect sperm quality and increase risk of genetic defects, particularly in populations with low AA such as smokers.