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.

Keywords::

• Catecholamines
• comet assay
• DNA damage
• epinephrine
• norepinephrine
• propranolol

Acknowledgment

This study is supported in part by a grant from the DOD (DAMD17-01-0373) and used the University of Pittsburgh Cancer Institute Animal Facility and was supported in part by award P30CA047904.

Declaration of interest : The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.