Mapping polycyclic aromatic hydrocarbon and aromatic amine-induced DNA damage in cancer-related genes at the sequence level
| Autor: | Annie Pao, Moon-shong Tang, Gerd P. Pfeifer, Jessica B. Zheng, Mikhail F. Denissenko, Haiying Li, James X. Chen, Yi Zheng, Wenwei Hu, Zhaohui Feng |
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| Rok vydání: | 2002 |
| Předmět: |
Enzyme complex
DNA Repair DNA damage Biology medicine.disease_cause Polymerase Chain Reaction chemistry.chemical_compound Amino Acids Aromatic medicine Escherichia coli Polycyclic Aromatic Hydrocarbons Gene Genetics Mutation Mutagenesis Public Health Environmental and Occupational Health Chromosome Mapping Genes p53 Chromatin Cell Transformation Neoplastic Genes ras Biochemistry chemistry Environmental Pollutants Carcinogenesis DNA DNA Damage |
| Zdroj: | International journal of hygiene and environmental health. 205(1-2) |
| ISSN: | 1438-4639 |
| Popis: | Genomic injury induced by environmental carcinogens, such as polycyclic aromatic hydrocarbons and aromatic amines, is the initial step that can trigger mutagenesis and carcinogenesis. In addition to the physico-chemical property of DNA damaging agents, several important factors such as primary sequence, chromatin structure, methylation, protein association, and transcriptional activity can affect not only the initial level and distribution of DNA damage but also the efficiency of repair. Therefore, mapping the DNA damage induced by environmental agents in cancer-related genes such as p53 and ras at the sequence level provides essential information for assessing their carcinogenic potential. Recently, using the E. coli nucleotide excision enzyme complex, UvrABC nucleases in combination with ligation-mediated polymerase chain reaction, we developed a method to map DNA damage in the p53 and ras genes. These studies led us to conclude that targeted DNA damage, in combination with growth selection, contributes greatly in shaping the mutation spectrum in these genes in human cancer. Here we present the rationale and details of this approach, typical experimental results and necessary precautions. |
| Databáze: | OpenAIRE |
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