• Title/Summary/Keyword: 7-Methylguanine

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Galangin의 MNNG 또는 Bleomycin유도 염색체 손상에 대한 억제효과

  • 허문영;윤여표;이병무
    • Proceedings of the Korean Society of Applied Pharmacology
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    • 1993.04a
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    • pp.99-99
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    • 1993
  • 본 연구에서는 이미 benzo(a)pyrene유도 소핵시험에서 뚜렷하게 소핵생성억제능을 보인 polyhydroxy flavonol유도체중의 하나인 Galangin에 대하여 C57BL/6 mice를 이용하여 N-methyl-N'-nitro-N-nitrosoguanidine(이하 MNNG)에 의해 유도된 소핵생성빈도에 미치는 영향을 살펴보고, spleen lymphocyte 배양을 통해 bleomycin 및 MNNG유도 염색체이상에 미치는 영향과 MNNG에 의해 유발된 DNA adduts중 biomarker로서 7-methylguanine형성에 대한 Galangin의 영향을 살펴봄으로서 ,Galangin의 유전독성 억제효과 및 작용기전에 대한 연구를 하고자하며 향후 Galangin을 모핵으로하는 cancer chemopreventive agent로의 유도체 합성에 기여하고자 한다.

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Methylation Status of the O6-Methylguanine-Deoxyribonucleic Acid Methyltransferase Gene Promoter in World Health Organization Grade III Gliomas

  • Yang, Seung-Heon;Kim, Yong-Hwy;Kim, Jin-Wook;Park, Chul-Kee;Park, Sung-Hye;Jung, Hee-Won
    • Journal of Korean Neurosurgical Society
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    • v.46 no.4
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    • pp.385-388
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    • 2009
  • Objective : We analyzed the methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) gene promoter in World Health Organization (WHO) grade III gliomas in association with other molecular markers to evaluate their prevalence. Methods : The samples of a total of 36 newly WHO grade III glioma patients including 19 anaplastic oligodendrogliomas (AO), 7 anaplastic oligoastrocytomas (AOA), and 10 anaplastic astrocytomas (AA) were analyzed. The methylation status of the MGMT gene promoter was confirmed by methylation-specific polymerase chain reaction. The 1p/19q chromosomal deletion status and EGFR amplification were assessed by Fluorescence In-Situ Hybridization. MGMT, EGFR, EGFRvlll, and p53 expression were analyzed by immunohistochemical staining. Results : The MGMT gene promoter was methylated in 32 (88.9%) and unmethylated in 4 (11.2%) Among them, all of the AO and AOA had methylated MGMT gene promoter without exception. Significant associations between MGMT gene promoter hypermethylation and 1p/19q deletion was observed (p=0.003). Other molecular markers failed to show significant associations between MGMT gene promoter statuses. Conclusion : There was extensive epigenetic silencing of MGMT gene in high grade gliomas with oligodendroglial component. Together with frequent 1p/19q co-deletion in oligodendroglial tumors, this may add plausible explanations supporting the relative favorable prognosis in oligodendroglial tumors compared with pure astrocytic tumors.

Promoter Methylation of MGMT Gene in Serum of Patients with Esophageal Squamous Cell Carcinoma in North East India

  • Das, Mandakini;Sharma, Santanu Kumar;Sekhon, Gaganpreet Singh;Saikia, Bhaskar Jyoti;Mahanta, Jagadish;Phukan, Rup Kumar
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.22
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    • pp.9955-9960
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    • 2014
  • Background: Promoter hypermethylation is a common event in human cancer. O6-methylguanine-DNA methyltransferase (MGMT) is a gene involved in DNA repair, which is methylated in a variety of cancers. We aimed to explore the methylation status of MGMT gene among the North Eastern population where esophageal cancer incidence and exposure to carcinogens like nitrosamines is high. Materials and Methods: A total of 100 newly diagnosed esophageal cancer cases along with equal number of age, sex and ethnicity matched controls were included in this study. Methylation specific PCR was used to determine the MGMT methylation status in serum samples. Results: Aberrant promoter methylation of the MGMT gene was detected in 70% of esophageal cancer cases. Hypermethylation of MGMT gene was found to be influenced by environmental factors like betel quid and tobacco which contain potent carcinogens like nitrosamines. Tobacco chewing and tobacco smoking habit synergistically with MGMT methylation elevated the risk for esophageal cancer development [adjusted OR=5.02, 95% CI=1.35-18.74; p=0.010 for tobacco chewing and Adjusted OR=3.00, 95% CI=1.22-7.36; p=0.014 for tobacco smoking]. Conclusions: Results suggest that the DNA hypermethylation of MGMT is an important mechanism for MGMT gene silencing resulting in esophageal cancer development and is influenced by the environmental factors. Thus MGMT hypermethylation can be used as a biomarker for esophageal cancer in high incidence region of North East India.

Role of P14 and MGMT Gene Methylation in Hepatocellular Carcinomas: a Meta-analysis

  • Li, Cheng-Cheng;Yu, Zhuang;Cui, Lian-Hua;Piao, Jin-Mei;Liu, Meng
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.16
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    • pp.6591-6596
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    • 2014
  • Background: This meta-analysis was performed to investigate the relationship between methylation of the P14 and O6-methylguanine-DNA methyltransferase (MGMT) genes and the risk of hepatocellular carcinoma (HCC). Materials and Methods: We searched PubMed, EMBASE, the Chinese Biomedical Database (CBM), and the China National Knowledge Infrastructure (CNKI) databases to identify relevant studies that analysed HCC tissues for P14 and MGMT gene methylation status; we then performed a meta-analysis. Odds ratios (ORs) and 95% confidence intervals (95%CIs) were calculated to evaluate the association between gene methylation and the risk of HCC. Results: Ten studies that assessed P14 gene methylation in 630 HCC tumour tissues and nine studies analysing MGMT methylation in 497 HCC tumour tissues met our inclusion criteria. Our meta-analysis revealed that the rate of P14 methylation was significantly higher in HCCs than in adjacent tissues (OR 3.69, 95%CI 1.63-8.35, p=0.002), but there was no significant difference in MGMT methylation between HCC and adjacent tissues (OR 1.76, 95%CI 0.55-5.64, p=0.34). A subgroup analysis according to ethnicity revealed that P14 methylation was closely related to the risk of HCC in Chinese and Western individuals (Chinese, OR 7.74, 95%CI 1.36-44.04, p=0.021; Western, OR 3.60, 95%CI 1.49-8.69, p=0.004). Furthermore, MGMT methylation was not correlated with the risk of HCC in Chinese individuals (OR 2.42, 95%CI 0.76-7.73, p=0.134). The combined rate of P14 methylation was 35% (95%CI 24-48%) in HCC tumour tissues and 11% (95%CI 4-27%) in adjacent tissues, whereas the combined rate of MGMT methylation was 15% (95%CI 6-32%) in HCC and 10% (95%CI 4-22%) in adjacent tissues. Conclusions: These results suggest that the risk of HCC is related to P14 methylation, but not MGMT methylation. Therefore, P14 gene methylation may be a potential biomarker for the diagnosis of HCC.