title: Chronic exposure to stress hormones promotes transformation and tumorigenicity of 3T3 mouse fibroblasts.
abstract: 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.
authors.affiliation: Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA 15237, USA.
authors.forename: Melanie S
authors.initials: MS
authors.lastname: Flint
authors.forename: Andrew
authors.initials: A
authors.lastname: Baum
authors.forename: Britteny
authors.initials: B
authors.lastname: Episcopo
authors.forename: Kelly Z
authors.initials: KZ
authors.lastname: Knickelbein
authors.forename: Angela J
authors.initials: AJ
authors.lastname: Liegey Dougall
authors.forename: William H
authors.initials: WH
authors.lastname: Chambers
authors.forename: Frank J
authors.initials: FJ
authors.lastname: Jenkins
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D015197:Carcinogenicity Tests; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D020552:Comet Assay; D004247:DNA / Q000187:drug effects; D004249:DNA Damage; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D041681:NIH 3T3 Cells; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000633:toxicity*; D011433:Propranolol / Q000494:pharmacology; D013315:Stress, Psychological / Q000503:physiopathology*
chemical_list: D000319:Adrenergic beta-Antagonists; D004247:DNA; D011433:Propranolol; D009638:Norepinephrine; D004837:Epinephrine