Lack of p53-Mediated G1 Arrest in Response to an Environmental Carcinogen
| Autor: | Qasim A. Khan, Anthony Dipple, Karen H. Vousden |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Cancer Research
Tumor suppressor gene Blotting Western Breast Neoplasms Biology Chrysenes Tumor Cells Cultured polycyclic compounds Humans Cigarette smoke Carcinogen Environmental Carcinogen Smoking G1 Phase DNA Neoplasm General Medicine Cell cycle Flow Cytometry 5-Methylchrysene Oncology G1 arrest Immunology Reactive metabolite Carcinogens Cancer research Tumor Suppressor Protein p53 DNA Damage |
| Zdroj: | Oncology. 57:258-264 |
| ISSN: | 1423-0232 0030-2414 |
| DOI: | 10.1159/000012040 |
| Popis: | The environmental carcinogen, 5-methylchrysene, is a component of cigarette smoke. Its reactive metabolite, anti-5-methylchrysene-1,2-dihydrodiol-3,4-epoxide (5-MeCDE) mainly reacts with the N2-position of guanine residues in the DNA molecule. In this study, we demonstrate that the tumor suppressor protein p53 is stabilized in response to DNA damage by 5-MeCDE but fails to induce the cells’ protective mechanism of G1 arrest in the human breast carcinoma cell line, MCF-7. In contrast, actinomycin D treatment of these cells did lead to G1 arrest. Western analyses revealed that, though both actinomycin D and 5-MeCDE treatment stabilized p53, only trace levels of p21waf1/cip1 were seen in the latter case. This lack of p21waf1/cip1 expression in 5-MeCDE-treated cells is attributed to a stealth characteristic of this environmental carcinogen that allows it to damage DNA and still escape the p53-mediated cellular defense mechanism of G1 arrest. |
| Databáze: | OpenAIRE |
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