LIGHT DURING DARKNESS AND BREAST CANCER PROGRESSION
Principal Investigator: David Blask
Abstract: The long-term goal of this research is to determine if light, present during darkness, is a risk factor for breast cancer progression. People in industrialized nations are being exposed to more artificial light during the night and the rate of breast cancer is increasing. The pineal gland hormone melatonin, which inhibits experimental human breast cancer growth, is produced during darkness; light present during darkness suppresses melatonin synthesis. The hypothesis to be tested is: Light, of the appropriate intensity, duration, timing and wavelength, present during darkness, stimulates breast cancer progression via melatonin suppression and a resultant disinhibition of tumor linoleic acid (LA) uptake and metabolism. The first aim is to measure the dose-response effects of exposure of nude female rats, bearing tissue-isolated estrogen receptor (ER)+ and progesterone receptor (PgR)+ MCF-7 human breast cancer xenografts, to different intensities of white light during darkness, on melatonin suppression in relation to tumor growth, LA metabolism and the expression of related growth signal transduction molecules (i.e., ER and PgR, melatonin receptor and cAMP). The second aim is to determine the dose-response effects of exposure of nude rats bearing MCF-7 xenografis in comparison with those bearing ER/PgR- MDA-MB-23 1 human breast cancer xenografts to different intensities of white light on melatonin suppression in relation to tumor growth. The third aim is to determine whether melatonin replacement will prevent the stimulative of effects of white light exposure during darkness on tumor growth, LA metabolism and the expression of related tumor growth signal transduction molecules. The fourth aim will test the effects of the duration and timing of light exposure during darkness on tumor growth and growth signal transduction events. This research may lead to the elucidation of "light-at-night" in conjunction with dietary fat intake as a new risk factor for breast cancer progression and to novel preventative measures for lowering breast cancer risk by combining modifications of indoor lighting and dietary fat intake with melatonin supplementation.
Funding Period: 2001-07-01 - 2005-06-30
more information: NIH RePORT
- Putting cancer to sleep at night: the neuroendocrine/circadian melatonin signalDavid E Blask
Laboratory of Chrono Neuroendocrine Oncology, Bassett Research Institute, Cooperstown, NY 13326, USA
Endocrine 27:179-88. 2005..Dietary melatonin supplementation working in concert with the endogenous melatonin signal has the potential to be a new preventive/therapeutic strategy to optimize the host/cancer balance in favor of host survival and quality of life...
- Circadian regulation of molecular, dietary, and metabolic signaling mechanisms of human breast cancer growth by the nocturnal melatonin signal and the consequences of its disruption by light at nightDavid E Blask
Laboratory of Chrono Neuroendocrine Oncology, Tulane University School of Medicine, New Orleans, LA, USA
J Pineal Res 51:259-69. 2011....
- Melatonin-depleted blood from premenopausal women exposed to light at night stimulates growth of human breast cancer xenografts in nude ratsDavid E Blask
Laboratory of Chrono Neuroendocrine Oncology, Bassett Research Institute, The Mary Imogene Bassett Hospital, Cooperstown, New York 13326, USA
Cancer Res 65:11174-84. 2005..These mechanistic studies are the first to provide a rational biological explanation for the increased breast cancer risk in female night shift workers...
- Light during darkness and cancer: relationships in circadian photoreception and tumor biologySamar A Jasser
Department of Neurology, Light Research Program, Thomas Jefferson University, 1025 Walnut Street, Suite 507, Philadelphia, PA 19107, USA
Cancer Causes Control 17:515-23. 2006..Continued rigorous empirical inquiry into the physiology and clinical implications of these habitual, integrated aspects of life is highly warranted at this time...
- Dietary factors and growth and metabolism in experimental tumorsLeonard A Sauer
Bassett Research Institute, Cooperstown, NY 13326, USA
J Nutr Biochem 18:637-49. 2007....
- Circadian stage-dependent inhibition of human breast cancer metabolism and growth by the nocturnal melatonin signal: consequences of its disruption by light at night in rats and womenDavid E Blask
Tulane Cancer Center and Louisiana Cancer Research Consortium, Tulane University School of Medicine, New Orleans, LA 70112, USA
Integr Cancer Ther 8:347-53. 2009..This biological mechanism may partially explain the higher risk of breast and other cancers in women working rotating night shifts and possibly others who also experience prolonged exposure to light at night...