2004 Fiscal Year Final Research Report Summary
The anticancer effects of 5-aza-2'deoxycytidine as a DNA demethylation agent on NNK-induced rat hepatocellular carcimonas
| Project/Area Number |
15590667
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
SASAKI Shigeru Sapporo Medical University, School of Medicine, Instructor, 医学部, 助手 (10305229)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Hiroyuki Sapporo Medical University, School of Medicine, Instructor, 医学部, 助手 (40332910)
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| Project Period (FY) |
2003 – 2004
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| Keywords | methylation / NNK / DNA array / hepatocellular carcinoma / DNA demethylation agent |
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| Research Abstract |
Hepatocellular tumors were induced in male Fischer 344 rats by treatment with the 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK) three times a week (50 mg/kg intraperitoneally injection) for 20 weeks. Based on histopathological analysis, these tumors were diagnosed as carcinomas (12 nodules/total 28 nodules) and adenomas (16 nodules/total 28 nodules).
RNA and DNA were isolated from these hepatocellular carcinomas. To determine gene expression changes associated with NNK exposure to genotoxic carcinogens, these RNA were subjected to microarray analysis. A number of genes were down-regulated by NNK exposure compared with controls. The methylation status of these down-regulated genes were determined by methylation-specific PCR (MSP). Overall, the promoter region hypermethylation of the p16 and E-cadherin genes were detected. The protein expression levels of p16 and E-cadherin were examined by immunohistochemical staining. The expression levels of these proteins were also down-regulated.
The anticancer effects of 5-aza-2'deoxycytidine once a week (1 mg/kg intraperitoneally injection) as a DNA demethylation agent on NNK-induced rat hepatocellular carcimonas were investigated. Our results suggested that 5-aza-2'deoxycytidine did not influence on the potency of hepatocarcinogenesis induced by NNK, the progression of hepatocellular carcinomas and the methylation status of p16 and E-cadherin genes methylated with NNK treatment.
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