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DNA修复酶N-甲基嘌呤-DNA糖基化酶(MPG)在星形细胞瘤中的表达

Expression of the DNA repair enzyme, N-methylpurine-DNA glycosylase (MPG) in astrocytic tumors.

作者信息

Kim Nam Keun, Ahn Jung Yong, Song Jihwan, Kim Jin Kyeoung, Han Jin Hee, An Hee Jung, Chung Hyung Min, Joo Jin Yang, Choi Joong Uhn, Lee Kyu Sung, Roy Rabindra, Oh Doyeun

机构信息

Department of Biochemistry, Institute for Clinical Research, College of Medicine, Pochon CHA University, Sungnam 463-712, S. Korea.

出版信息

Anticancer Res. 2003 Mar-Apr;23(2B):1417-23.

Abstract

BACKGROUND

DNA is continuously damaged due to exposure to alkylating compounds or oxygen free radicals generated during normal cellular metabolism as well as to environmental mutagens. Several studies have shown that N-methylpurine-DNA-glycosylase (MPG) mRNA levels were lower in adult brain than in other tissues. Terminally differentiated and nonproliferating cells have a lower DNA repair capacity than proliferating cells from various organs, embryo, ovary and testis. If the DNA repair are not efficient, the damaged DNA may lead to tumorigenesis or cell death. This study was designed to investigate the association of tumorigenesis with MPG in astrocytic tumors.

MATERIALS AND METHODS

MPG mRNA expression and localization in astrocytic tumors and tumor-adjacent brain tissues was examined by reverse transcriptase-polymerase chain reaction (RT-PCR) and RNA in situ hybridization. The expression and intracellular localization of MPG protein was determined by immunohistochemistry.

RESULTS

MPG mRNA expression in RT-PCR was slightly higher in astrocytic tumor tissues than in brain tissues adjacent to tumor and in astrocytic tumor tissues, regardless of the tumor grades. MPG protein localization in immunohistochemical study was detected only in the nucleus of all tumor tissues. Interestingly, in brain tissues adjacent to tumor, immunohistochemical staining for MPG was not observed either in the nucleus or the cytoplasm. However, we could not detect MPG protein in the brain tissues adjacent to the tumor although MPG mRNA was detected in the tissues.

CONCLUSION

These results suggest an MPG's role in human astrocytic tumors and raise the possibility that the altered MPG expression and intracellular localization could be associated with astrocytic tumorigenesis.

摘要

背景

由于暴露于正常细胞代谢过程中产生的烷基化化合物或氧自由基以及环境诱变剂,DNA会不断受到损伤。多项研究表明,成年大脑中N - 甲基嘌呤 - DNA - 糖基化酶(MPG)的mRNA水平低于其他组织。终末分化且不增殖的细胞比来自各种器官、胚胎、卵巢和睾丸的增殖细胞具有更低的DNA修复能力。如果DNA修复效率不高,受损的DNA可能导致肿瘤发生或细胞死亡。本研究旨在探讨MPG与星形细胞瘤发生的关联。

材料与方法

通过逆转录 - 聚合酶链反应(RT - PCR)和RNA原位杂交检测MPG mRNA在星形细胞瘤及肿瘤邻近脑组织中的表达和定位。通过免疫组织化学确定MPG蛋白的表达和细胞内定位。

结果

RT - PCR检测显示,MPG mRNA在星形细胞瘤组织中的表达略高于肿瘤邻近脑组织,且在星形细胞瘤组织中,与肿瘤分级无关。免疫组织化学研究中,MPG蛋白定位仅在所有肿瘤组织的细胞核中检测到。有趣的是,在肿瘤邻近脑组织中,无论是细胞核还是细胞质中均未观察到MPG的免疫组织化学染色。然而,尽管在肿瘤邻近脑组织中检测到了MPG mRNA,但未检测到MPG蛋白。

结论

这些结果提示了MPG在人类星形细胞瘤中的作用,并增加了MPG表达和细胞内定位改变可能与星形细胞瘤发生相关的可能性。

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