The Relationship Between DNA Repair Systems and Carcinogenesis in Oral Epithelium

• Main Authors: Sung-Shian Huang, 黃頌銜
• Other Authors: Shin-Fang Yang
• Format: Others
• Language: zh-TW
• Published: 2003
• Online Access: http://ndltd.ncl.edu.tw/handle/04249382605541664288

碩士 === 國立陽明大學 === 口腔生物研究所 === 91 === The maintenance of genome integrity and fidelity is essential for the proper function and survival of all organisms. This task is particularly daunting due to constant assault on the DNA by genotoxic agents (both endogenous and exogenous), nucleotide misincorporation during DNA replication, and the intrinsic biochemical instability of the DNA itself. Failure to repair DNA lesions may result in blockages of transcription and replication, mutagenesis, and/or cellular cytotoxicity. In humans, DNA damage has been shown to be involved in a variety of genetically inherited disorders, in aging, and in carcinogenesis. All eukaryotic cells have evolved a multifaceted response to counteract the potentially deleterious effects of DNA damage. For maintain the genome integrity and fidelity. DNA repair processes are classified into pathways responsible for repairing specific classes of DNA damage, although recent data indicated that some proteins function in multiple pathways. Base excision repair (BER) occurs through excision of a damaged region, followed by fill-in repair synthesis using the opposite strand as a template. Mismatch repair (MMR) operates on base mismatched and small loop-outs that arising during replication by misincorporation or slippage on the template strand. Nucleotide excision repair (NER) removes photoproducts from u.v. radiaton and bulky adducts from a multiple of chemicals. DNA double-strand breaks may be rectified by either homologous recombination repair (HRR) and nonhomologous end joining pathways (NHEJ) where both strands of the DNA duplex are damaged. As a step in providing a basis for epidemiology studies to relate DNA repair systems on oral cancer, this study initiate to investigate the main DNA repair genes in each system. A total of 39 patients with the diagnosis of oral cancer and 27 healthy controls were immunostained for protein expression of OGG1 (BER), APE (BER), XPA (NER), hMSH2 (MMR), hMLH1 (MMR), ATM (HRR & NHEJ), and RAD51 (HRR). The histopathological findings suggest that themain DNA repair pathway in oral cancer is BER; however, elevation of both NER and MMR was also found. This study also demonstrated that arecoline, a major pharmacologically active alkaloid of areca nut, affected the cell viability within 200-800µM. However, DNA repair systems in the arecoline treatment of cell culture were not significantly changed in western blotting. The negative biological significance in this assay may be correlated with time courses. In this study, we suggest that BER and MMR repair systems might be the major DNA repair system in oral tissue.