Nitric oxide inhibits DNA-adduct excision in nucleotide excision repair
Nitric oxide inhibits DNA-adduct excision in nucleotide excision repair
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DOI：
10.1016/j.freeradbiomed.2004.01.011
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发表时间：
2004-04-15
影响因子：
7.4
通讯作者：
Jan, KY
中科院分区：
文献类型：
--
作者：
Chien, YH;Bau, DT;Jan, KY
在慢性炎症中持续诱导一氧化氮（NO）可能是致突变的，通过DNA损伤诱导和/或DNA修复抑制。虽然有很好的证据表明NO可以引起DNA损伤，但NO如何参与DNA修复仍然是一个谜。用DNA合成抑制剂在彗星试验中积累DNA链断裂。我们发现NO和过氧亚硝酸盐抑制UVC，4-硝基喹啉1-氧化物损伤的人成纤维细胞中的DNA加合物切除。苯并[a]芘二氢二醇环氧化物、顺铂或丝裂霉素C，但不与甲磺酸甲酯。用亚砷酸盐处理细胞增加NO产生，也抑制UVC诱导的DNA加合物切除。4-硝基喹啉1-氧化物、苯并[a]芘二氢二醇环氧化物、顺铂和丝裂霉素C，但甲烷磺酸甲酯不能。H2 O2、亚硝基红酸钠或3-morpholinosydnonimine。NO合酶抑制剂和NO清除剂可降低砷对DNA加合物切除的抑制作用。从用亚硝基红酸钠、二亚丙基三胺NONOate、3-morpholinosynonimine或亚砷酸盐预处理的成纤维细胞制备的核提取物在切除由UVC和顺铂诱导的DNA加合物中也显示出降低的活性，但不是由甲磺酸甲酯或H2 O2加Fe诱导的。这些结果是一致的概念，NO，过氧亚硝酸盐，亚砷酸盐抑制DNA加合物切除核苷酸切除修复，但不是在碱基切除修复。(C)2004年爱思唯尔公司All rights reserved.
Sustained induction of nitric oxide (NO) in chronic inflammation may be mutagenic, through DNA damage induction and/or DNA repair inhibition. Although there is good evidence that NO can cause DNA damage, how NO is involved in DNA repair remains elusive. By using DNA synthesis inhibitors to accumulate DNA strand breaks in comet assay. we show that NO and peroxynitrite inhibit DNA-adduct excision in human fibroblasts damaged by UVC, 4-nitroquinoline 1-oxide. benzo[a]pyrene dihydrodiol epoxide, cisplatin, or mitomycin C, but not with methyl methane sulfonate. Treating cells with arsenite increased NO production and also inhibited the DNA-adduct excision induced by UVC. 4-nitroquinoline 1-oxide, benzo[a]pyrene dihydrodiol epoxide, cisplatin, and mitomycin C, but not by methyl methane sulfonate. H2O2, sodium nitrosoprusside, or 3-morpholinosydnonimine. Arsenite inhibition of DNA-adduct excision was decreased by NO synthase inhibitors and NO scavengers. The nuclear extract prepared from fibroblasts pretreated with sodium nitrosoprusside, dipropylenetriamine NONOate, 3-morpholinosydnonimine, or arsenite also showed decreased activity in excising the DNA adducts induced by U VC and cisplatin but not by methyl methane sulfonate or H2O2 Plus Fe. These results are consistent with the notion that NO, peroxynitrite, and arsenite inhibit the DNA-adduct excision in nucleotide excision repair but not that in base excision repair. (C) 2004 Elsevier Inc. All rights reserved.