Chronic exposure to stress hormones promotes transformation and tumorigenicity of 3T3 mouse fibroblasts
| Autor: | Britteny Episcopo, Andrew Baum, Melanie S. Flint, William H. Chambers, Kelly Z. Knickelbein, Angela Liegey Dougall, Frank J. Jenkins |
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| Rok vydání: | 2012 |
| Předmět: |
Genome instability
medicine.medical_specialty Epinephrine Carcinogenicity Tests Physiology DNA damage Adrenergic beta-Antagonists Mice Nude Propranolol Biology Article Norepinephrine (medication) Mice Norepinephrine Behavioral Neuroscience Internal medicine medicine Animals Mice Inbred BALB C Dose-Response Relationship Drug Endocrine and Autonomic Systems DNA Comet assay Psychiatry and Mental health Cell Transformation Neoplastic Neuropsychology and Physiological Psychology Endocrinology Tumor progression Disease Progression NIH 3T3 Cells Female Comet Assay Stress Psychological DNA Damage medicine.drug Hormone |
| Zdroj: | Stress. 16:114-121 |
| ISSN: | 1607-8888 1025-3890 |
| DOI: | 10.3109/10253890.2012.686075 |
| Popis: | Epinephrine and norepinephrine are produced during psychological stress and can directly bind to cells to induce DNA damage. These effects may have more long-lasting consequences such as DNA mutations resulting in an increased potential for cellular transformation and/or tumor progression. This study examined the molecular effects of a chronic (24 h) in vitro exposure to these stress hormones on murine 3T3 cells. Long exposures (24 h) in dose-response experiments with norepinephrine or epinephrine induced significant increases in DNA damage in treated cells compared to that of untreated controls as measured by the alkaline comet assay. Pre-treatment with a blocking agent (the β-adrenergic receptor antagonist propranolol) eliminated this increase in damage. In addition, both norepinephrine and epinephrine increased cellular transformation, as assessed by growth in soft agar, and 3T3 cells pre-treated with either norepinephrine or epinephrine induced a more rapid onset of tumors and more aggressive tumor growth in nude mice. In summary, incubation of 3T3 cells with catecholamines results in long-term DNA damage as measured by increased transformed phenotypes and tumor progression, indicating that they are important mediators of stress effects on genomic instability and vulnerability to tumor formation. |
| Databáze: | OpenAIRE |
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