Melatonin-depleted blood from premenopausal women exposed to light at night stimulates growth of human breast cancer xenografts in nude rats
Melatonin-depleted blood from premenopausal women exposed to light at night stimulates growth of human breast cancer xenografts in nude rats
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DOI：
10.1158/0008-5472.can-05-1945
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发表时间：
2005-12-01
期刊：
影响因子：
11.2
通讯作者：
Zalatan, F
中科院分区：
文献类型：
--
作者：
Blask, DE;Brainard, GC;Zalatan, F
女性夜班工作者患乳腺癌的风险增加被认为是由于夜间暴露在光线下抑制了松果体褪黑激素的产生。将携带大鼠肝癌或人乳腺癌异种移植物的大鼠暴露于每12小时黑暗期强度增加的白色荧光（0-345 μ W/cm（2））中，导致夜间褪黑激素血液水平的剂量依赖性抑制，并刺激肿瘤生长和亚油酸摄取/代谢为促有丝分裂分子13-羟基十八碳二烯酸。从健康的绝经前女性志愿者中采集静脉血样，这些志愿者在白天、夜间或在眼部明亮的白色荧光灯照射90分钟后，以580 μ W/cm（2）（即，2，800 lx）。与白天收集的褪黑激素缺乏的血液灌注的肿瘤相比，人乳腺癌异种移植物和大鼠肝癌原位灌注，夜间收集的富含褪黑激素的血液，表现出显着抑制增殖活性和亚油酸的摄取/代谢。用褪黑激素缺乏血液灌注的肿瘤在夜间眼部暴露于光下后收集，表现出高肿瘤增殖活性的白天模式。这些结果首次表明，在黑暗中暴露于光的肿瘤生长反应是强度依赖性的，并且人类夜间的昼夜褪黑激素信号不仅抑制人类乳腺癌生长，而且这种作用被夜间短期眼部暴露于明亮的白色光所消除。这些机制研究首次为女性夜班工人乳腺癌风险增加提供了合理的生物学解释。
The increased breast cancer risk in female night shift workers has been postulated to result from the suppression of pineal melatonin production by exposure to light at night. Exposure of rats bearing rat hepatomas or human breast cancer xenografts, to increasing intensities of white fluorescent light during each 12-hour dark phase (0-345 mu W/cm(2)) resulted in a dose-dependent suppression of nocturnal melatonin blood levels and a stimulation of tumor growth and linoleic acid uptake/metabolism to the mitogenic molecule 13-hydroxyoctadecadienoic acid. Venous blood samples were collected from healthy, premenopausal female volunteers during either the daytime, nighttime, or nighttime following 90 minutes of ocular bright, white fluorescent light exposure at 580 mu W/cm(2) (i.e., 2,800 lx). Compared with tumors perfused with daytime collected melatonin-deficient blood, human breast cancer xenografts and rat hepatomas perfused in situ, with nocturnal, physiologically melatonin-rich blood collected during the night, exhibited markedly suppressed proliferative activity and linoleic acid uptake/metabolism. Tumors perfused with melatonin-deficient blood collected following ocular exposure to light at night exhibited the daytime pattern of high tumor proliferative activity. These results are the first to show that the tumor growth response to exposure to light during darkness is intensity dependent and that the human nocturnal, circadian melatonin signal not only inhibits human breast cancer growth but that this effect is extinguished by short-term ocular exposure to bright, white light at night. These mechanistic studies are the first to provide a rational biological explanation for the increased breast cancer risk in female night shift workers.