DNA Hypermethylation of Promoter of Gene p53 and p16 in Arsenic-Exposed People with and without Malignancy
| Autor: | Subhankar Das, Sarbari Lahiri, Mausumi Gupta, Debdutta Chatterjee, Uma B. Dasgupta, Nilima Ghosh, Debendranath GuhaMazumder, Sarmishtha Chanda, Utpal Chaudhuri |
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| Rok vydání: | 2005 |
| Předmět: |
Adult
Male Skin Neoplasms Adolescent chemistry.chemical_element Biology Toxicology medicine.disease_cause Arsenic law.invention chemistry.chemical_compound law Arsenic Poisoning medicine Humans Genes Tumor Suppressor Promoter Regions Genetic Gene Polymerase chain reaction integumentary system Genes p16 Promoter Methylation DNA Methylation Middle Aged Genes p53 Molecular biology chemistry DNA methylation Cancer research Female Carcinogenesis Water Pollutants Chemical DNA |
| Zdroj: | Toxicological Sciences. 89:431-437 |
| ISSN: | 1096-0929 1096-6080 |
| DOI: | 10.1093/toxsci/kfj030 |
| Popis: | Chronic Arsenic exposure is known to produce arsenicosis and cancer. To ascertain whether perturbation of methylation plays a role in such carcinogenesis, the degree of methylation of p53 and p16 gene in DNA obtained from blood samples of people chronically exposed to arsenic and skin cancer subjects was studied. Methylation specific restriction endonuclease digestion followed by polymerase chain reaction (PCR) of gene p53 and bisulfite treatment followed by methylation sensitive PCR of gene p16 have been carried out to analyse the methylation status of the samples studied. Significant DNA hypermethylation of promoter region of p53 gene was observed in DNA of arsenic exposed people compared to control subjects. This hypermethylation showed a dose response relationship. Further, hypermethylation of p53 gene was also observed in arsenic induced skin cancer patients compared to subjects having skin cancer unrelated to arsenic though not at significant level. However a small subgroup of cases showed hypomethylation with high arsenic exposure. Significant hypermethylation of gene p16 was also observed in cases of arsenicosis exposed to high level of arsenic. In man arsenic has the ability to alter DNA methylation pattern in gene p53 and p16 which are important in carcinogenesis. |
| Databáze: | OpenAIRE |
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