Elevated oxidative stress and DNA damage and repair levels in urinary bladder carcinomas associated with Schistosomiasis
Elevated oxidative stress and DNA damage and repair levels in urinary bladder carcinomas associated with Schistosomiasis
复制标题
DOI：
10.1002/ijc.23547
复制
发表时间：
2008-08-01
影响因子：
6.4
通讯作者：
Wanibuchi, Hideki
中科院分区：
文献类型：
--
作者：
Salim, Elsayed I.;Morimura, Keiichirou;Wanibuchi, Hideki
为了阐明血吸虫病相关膀胱尿路上皮癌（UCs）发生的潜在机制，我们采用免疫组化方法分析了氧化应激标志物、DNA单链断裂（ssDNA）之间的关系，ssDNA也可以测量DNA中碱基损伤和凋亡水平，和埃及患者膀胱癌中一氧化氮合酶水平的DNA修复基因的表达与血吸虫感染或无血吸虫感染。与非血吸虫癌相比，在与血吸虫病相关的鳞状细胞癌和UC中发现8-羟基-2 '-脱氧鸟苷（8-OHdG）水平显著升高。这伴随着DNA修复基因、8-氧代鸟嘌呤-DNA-糖基化酶和脱嘌呤/脱嘧啶核酸内切酶的强烈过度表达，以及ssDNA形成水平的增加。诱导型一氧化氮合酶（iNOS），这是已知的间接相关的氧化应激的表达水平较高的血吸虫比非血吸虫癌。然而，内皮型一氧化氮合酶的表达略强于非血吸虫性血吸虫癌。总之，这些研究结果表明，血吸虫感染和氧化应激水平的增加伴随着连续的DNA损伤和修复的UC之间的强相关性，所有直接与升高的诱导型一氧化氮合酶。(C)2008 Wiley-Liss，Inc.
To cast light on mechanisms underlying development of urothelial carcinomas (UCs) of the urinary bladder associated with Schistosomiasis, we mummohistochemically analyzed the relationship between oxidative stress markers, DNA single strand breaks (ssDNA) which could also measure the levels of base damage and apoptosis in DNA, and expression of DNA repair genes with levels of nitric oxide synthases in bladder carcinomas of Egyptian patients with or without Schistosoma hematobium infection. Marked elevation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels was found in squamous cell carcinomas and UCs associated with Schistosomiasis when compared with non-Schistosomal carcinomas. This was accompanied by strong over expression of the DNA-repair genes, 8-oxoguanine-DNA-glycosylase and apurinic/apyrimidinic endonuclease, as well as increased formation levels of ssDNA. Expression levels of inducible nitric oxide synthase (iNOS) which is known to be indirectly related to oxidative stress was higher in Schistosomal than in the non-Schistosomal carcinomas. However, expression of endothelial nitric oxide synthase was slightly stronger in non-Schistosomal than in the Schistosomal carcinomas. In conclusion, these findings suggest a strong correlation between Schistosoma haematobium infection and increased levels of oxidative stress accompanied by a continuous DNA damage and repair in UCs, all directly correlating with elevated iNOS. (C) 2008 Wiley-Liss, Inc.