Limited repair of 8-hydroxy-7,8-dihydroguanine residues in human testicular cells
Limited repair of 8-hydroxy-7,8-dihydroguanine residues in human testicular cells
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DOI：
10.1093/nar/gkg216
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发表时间：
2003-02-15
影响因子：
14.9
通讯作者：
Brunborg, G
中科院分区：
文献类型：
--
作者：
Olsen, AK;Duale, N;Brunborg, G
睾丸DNA的氧化损伤与精液质量差、生育能力降低以及死胎和出生缺陷风险增加有关。这些DNA损伤主要通过碱基切除修复来去除。人和大鼠睾丸细胞的细胞提取物和大鼠雄性生殖细胞（初级精母细胞、圆形精子细胞和伸长/伸长精子细胞）的三个富集群体均显示出5-羟基胞嘧啶、胸腺嘧啶乙二醇和2，6-二氨基-4-羟基-5-甲酰胺嘧啶的有效切除/切割。含有8-氧代-7，8-二氢鸟嘌呤的DNA被人睾丸细胞提取物切除得很差，尽管8-氧代鸟嘌呤-DNA糖基化酶-1（hOGG 1）存在于人睾丸细胞中，其水平在13个个体之间变化显著。这种切除与人单核血细胞提取物一样低。内切核酸酶III同源物-1（NTH 1），它切除氧化嘧啶，水平较高，在睾丸比两个物种的体细胞。用碱性洗脱和彗星试验检测由甲酰胺嘧啶-DNA糖基化酶（Fpg）或核酸内切酶III（Nth）识别的损伤的细胞修复研究。与酶活性一致，人睾丸细胞表现出对Fpg敏感性病变的去除较差，但对Nth敏感性病变的修复有效。大鼠睾丸细胞有效地修复Fpg和Nth敏感的病变。总之，人类睾丸细胞修复重要的氧化DNA损伤的能力有限，这可能导致生殖功能受损和新生突变。
Oxidative damage in testicular DNA is associated with poor semen quality, reduced fertility and increased risk of stillbirths and birth defects. These DNA lesions are predominantly removed by base excision repair. Cellular extracts from human and rat testicular cells and three enriched populations of rat male germ cells (primary spermatocytes, round spermatids and elongating/elongated spermatids) all showed proficient excision/incision of 5-hydroxycytosine, thymine glycol and 2,6-diamino-4-hydroxy-5-formamidopyrimidine. DNA containing 8-oxo-7,8-dihydroguanine was excised poorly by human testicular cell extracts, although 8-oxoguanine-DNA glycosylase-1 (hOGG1) was present in human testicular cells, at levels that varied markedly between 13 individuals. This excision was as low as with human mononuclear blood cell extracts. The level of endonuclease III homologue-1 (NTH1), which excises oxidised pyrimidines, was higher in testicular than in somatic cells of both species. Cellular repair studies of lesions recognised by formamidopyrimidine-DNA glycosylase (Fpg) or endonuclease III (Nth) were assayed with alkaline elution and the Comet assay. Consistent with the enzymatic activities, human testicular cells showed poor removal of Fpg-sensitive lesions but efficient repair of Nth-sensitive lesions. Rat testicular cells efficiently repaired both Fpg- and Nth-sensitive lesions. In conclusion, human testicular cells have limited capacity to repair important oxidative DNA lesions, which could lead to impaired reproduction and de novo mutations.