The Roles of Benzo(a)Pyrene in Regulating DNA Damage Repair
| Autor: | Tzu-Fen Chen, 陳姿分 |
|---|---|
| Rok vydání: | 2008 |
| Druh dokumentu: | 學位論文 ; thesis |
| Popis: | 96 Benzo[a]pyrene (BaP) is a member of polycyclic aromatic hydrocarbons (PAHs), which are environmental pollutants and may contribute to the development of human cancer. It has been shown that BaP metabolites are able to bind covalently with DNA to form unstable adducts and induce DNA damage. However, the role of BaP in regulating DNA repair is unclear. In this study, we investigated whether BaP could interfere with DNA repair in H1299, a p53-null non-small cell lung cancer cell line. We found that nucleotide excision repair (NER), but not non-homologous end-joining was repressed in H1299 cells after treatment of 50 ?嵱 BaP for 2 weeks. Fluoranthene, another PAH, had no apparent effects on both NER and NHEJ repair. We also showed that BaP could inhibit p53-mediated NER activity when the p53 expression was restored in H1299 cells. Therefore, BaP could inhibit NER through p53-dependent and p53-independent pathways. We next examined whether cell growth was affected due to BaP-mediated repression of NER. Cell number counting and MTT assays showed that 24-hr exposure of BaP did not alter cell growth. However, one and two weeks incubation of H1299 cells with BaP resulted in apparent growth suppression demonstrated by colony formation assays. Taken together, these data suggested that BaP could repress nucleotide excision repair and inhibit cell growth after a longer period (1 to 2 weeks) of exposure. |
| Databáze: | Networked Digital Library of Theses & Dissertations |
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