Chronic exposure to stress hormones promotes transformation and tumorigenicity of 3T3 mouse fibroblasts.
Chronic exposure to stress hormones promotes transformation and tumorigenicity of 3T3 mouse fibroblasts.
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DOI：
10.3109/10253890.2012.686075
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发表时间：
2013-01
期刊：
影响因子：
--
通讯作者：
Jenkins FJ
中科院分区：
文献类型：
--
作者：
Flint MS;Baum A;Episcopo B;Knickelbein KZ;Liegey Dougall AJ;Chambers WH;Jenkins FJ
肾上腺素和去甲肾上腺素在心理应激时产生，可直接与细胞结合，诱导DNA损伤。这些影响可能有更持久的后果，如DNA突变导致细胞转化和/或肿瘤进展的潜力增加。本研究检测了慢性（24小时）体外暴露于这些应激激素对小鼠3T3细胞的分子效应。在剂量反应实验中，长时间暴露在去甲肾上腺素或肾上腺素中（24小时），与未处理的对照组相比，处理细胞的DNA损伤显著增加。用阻断剂（β-肾上腺素能受体拮抗剂心得安）进行预处理可以消除这种损伤的增加。此外，通过在软琼脂中生长来评估，去甲肾上腺素和肾上腺素都增加了细胞转化，在裸鼠中，用去甲肾上腺素或肾上腺素预处理的3T3细胞诱导了更快的肿瘤发作和更强的肿瘤生长。总之，儿茶酚胺与3T3细胞孵育会导致长期DNA损伤，通过增加转化表型和肿瘤进展来测量，表明儿茶酚胺是应激对基因组不稳定性和肿瘤形成易感性影响的重要介质。
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.
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DOI：
10.1111/j.1349-7006.2002.tb01313.x
发表时间：
2002-07
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Hasegawa H;Saiki I
通讯作者：
Saiki I
影响因子：
5
作者：
Lillberg, K;Verkasalo, PK;Koskenvuo, M
通讯作者：
Koskenvuo, M
影响因子：
4.8
作者：
Nilsson, Monique B.;Armaiz-Pena, Guillermo;Sood, Anil K.
通讯作者：
Sood, Anil K.
影响因子：
15.1
作者：
Lutgendorf, Susan K.;DeGeest, Koen;Dahmoush, Laila;Farley, Donna;Penedo, Frank;Bender, David;Goodheart, Michael;Buekers, Thomas E.;Mendez, Luis;Krueger, Gina;Clevenger, Lauren;Lubaroff, David M.;Sood, Anil K.;Cole, Steve W.
通讯作者：
Cole, Steve W.
影响因子：
5.5
作者：
Li, Jun;Yan, Biao;Chen, Yi-Han
通讯作者：
Chen, Yi-Han