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The Role of Environmental Lighting and Circadian Disruption in Cancer and Other Diseases

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The Role of Environmental Lighting and Circadian Disruption in Cancer and Other Diseases Meeting Report: The Role of Environmental Lighting and Circadian Disruption in Cancer and Other Diseases The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Stevens, Richard G., David E. Blask, George C. Brainard, Johnni Hansen, Steven W. Lockley, Ignacio Provencio, Mark S. Rea, and Leslie Reinlib. 2007. Meeting report: The role of environmental lighting and circadian disruption in cancer and other diseases. Environmental Health Perspectives 115(9): 1357-1362. Published Version doi:10.1289/ehp.10200 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:4621603 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA Research Meeting Report: The Role of Environmental Lighting and Circadian Disruption in Cancer and Other Diseases Richard G. Stevens,1 David E. Blask,2 George C. Brainard,3 Johnni Hansen,4 Steven W. Lockley,5 Ignacio Provencio,6 Mark S. Rea,7 and Leslie Reinlib 8 1University of Connecticut Health Center, Farmington, Connecticut, USA; 2Bassett Research Institute, Cooperstown, New York, USA; 3Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania, USA; 4Danish Cancer Society, Copenhagen, Denmark; 5Harvard Medical School, Boston, Massachusetts, USA; 6Department of Biology, University of Virginia, Charlottesville, Virginia, USA; 7Lighting Research Center, Rensselaer Polytechnic Institute, Troy, New York, USA; 8Division of Extramural Research and Training, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA these hypotheses has a solid base and is Light, including artificial light, has a range of effects on human physiology and behavior and can currently moving forward rapidly. therefore alter human physiology when inappropriately timed. One example of potential light- For these reasons, the National Institute induced disruption is the effect of light on circadian organization, including the production of sev- of Environmental Health Sciences (NIEHS) eral hormone rhythms. Changes in light–dark exposure (e.g., by nonday occupation or transmeridian on 14–15 September 2006 convened a work- travel) shift the timing of the circadian system such that internal rhythms can become desynchro- shop of a diverse group of scientists to con- nized from both the external environment and internally with each other, impairing our ability to sider how best to conduct research on sleep and wake at the appropriate times and compromising physiologic and metabolic processes. possible connections between lighting and Light can also have direct acute effects on neuroendocrine systems, for example, in suppressing mela- health. The potential for circadian disruption, tonin synthesis or elevating cortisol production that may have untoward long-term consequences. particularly light exposures at night, to con- For these reasons, the National Institute of Environmental Health Sciences convened a workshop of tribute to the etiology of cancer or other dis- a diverse group of scientists to consider how best to conduct research on possible connections eases has become an urgent question in part between lighting and health. According to the participants in the workshop, there are three broad because a large and increasing segment of the areas of research effort that need to be addressed. First are the basic biophysical and molecular population of industrialized nations is work- genetic mechanisms for phototransduction for circadian, neuroendocrine, and neurobehavioral regu- ing nonday shifts (Rajaratnam and Arendt lation. Second are the possible physiologic consequences of disrupting these circadian regulatory 2001). It is also important because the popu- processes such as on hormone production, particularly melatonin, and normal and neoplastic tissue lation in general has been reducing its expo- growth dynamics. Third are effects of light-induced physiologic disruption on disease occurrence and sure to dark over recent decades as reflected prognosis, and how prevention and treatment could be improved by application of this knowledge. in a decrease in the average duration of sleep Key words: breast cancer, circadian rhythms, clock genes, lighting, melatonin, phototransduction, (National Sleep Foundation 2005). pineal gland. Environ Health Perspect 115:1357–1362 (2007). doi:10.1289/ehp.10200 available via http://dx.doi.org/ [Online 14 June 2007] Definitions “Diurnal rhythms” denote recurring daily 24-hr rhythms in physiology, behavior, or Humans have evolved over millions of years in light–dark exposure shift the timing of the metabolism under entrainment conditions and adapted to a solar day of approximately circadian system such that internal rhythms but not necessarily under constant, non- 12 hr of light and 12 hr of dark, latitude and can become desynchronized from both the entrainment conditions. “Entrainment” is the season permitting. Our ability to artificially external environment and internally with each synchronization of a rhythm by a repetitive light the night began about 250,000 years ago other, impairing our ability to sleep and wake signal (e.g., the light–dark cycle). “Circadian when we discovered how to use fire. Candles at the appropriate times and compromising rhythms” (e.g., melatonin production) denote were introduced about 5,000 years ago, and metabolic processes. Light can also have direct those endogenous, near 24-hr physiologic, gas street lighting was possible beginning in acute effects on neuroendocrine systems, for metabolic, or behavioral rhythms that persist the mid-1700s. However, only in the last example, in suppressing melatonin synthesis or under constant nonentrainment conditions 120 years has environmental illumination elevating cortisol production that may have (e.g., constant darkness) and are presumably begun to change on a pervasive scale for the untoward long-term consequences. driven by the molecular clockwork mecha- masses of people through the introduction of There is limited but thus far generally con- nism in the suprachiasmatic nucleus (SCN) electric lighting. One of the defining features sistent evidence in support of the hypothesis and peripheral tissues (Dunlap et al. 2004). of the built environment in the modern world that altered lighting can play a role in breast is this artificial lighting. Electricity has made it cancer causation (Blask et al. 2005a; Hansen Background possible to light the inside of large buildings 2001; Stevens 1987, 2006), and there is grow- Circadian rhythms—master and peripheral and light the night for work, recreation, and ing interest in a lighting and/or sleep connec- clocks. The hypothalamic SCN is the master security. The benefits of this lighting are obvi- tion to other conditions such as prostate cancer circadian pacemaker in mammals, driving ous and enormous. It has become apparent, (Kubo et al. 2006; Stevens et al. 1992), obesity however, that although of obvious benefit, it (Spiegel et al. 2004), diabetes (Spiegel et al. Address correspondence to R.G. Stevens, Department may not be completely innocuous. Light, 2005), and depression (Srinivasan et al. 2006). of Community Medicine, UConn Health Center, 263 including artificial light, can be potent in regu- It may not be entirely coincidental that the Farmington Ave., Farmington, CT 06030-6325 USA. lating human physiology and behavior and can dramatic increases in risk of breast and prostate Telephone: (860) 679-5475. Fax: (860) 679-5464. therefore alter human physiology when in- cancers, and of obesity and early onset diabetes E-mail: [email protected] This work was supported by NIEHS and NIEHS appropriately timed. One example of potential have mirrored the dramatic changes in the grant ES11659. light-induced disruption is the effect of light amount and pattern of artificial light generated The authors declare they have no competing on circadian organization, including the pro- during the night and day in modern societies financial interests. duction of several hormone rhythms. Changes over recent decades. The science underlying Received 28 February 2007; accepted 14 June 2007. Environmental Health Perspectives • VOLUME 115 | NUMBER 9 | September 2007 1357 Stevens et al. circadian rhythms in behavior, physiology, existing only in the eyes of frogs and mammals Only 47% of aged mice forced to phase endocrinology, and metabolism (Ko and (Cahill et al. 1991; Tosini and Menaker 1996). advance 6 hr once per week survived the Takahashi 2006; Moore and Leak 2001). The In the late 1990s, however, the use of biolumi- experiment compared with an 83% survival core genetic apparatus of the clock mecha- nescent reporter proteins expressed under the rate in an unshifted age-matched control nism is being rapidly revealed and thus far control of clock gene promoters revealed that group. Aged mice subjected to weekly 6-hr appears to be based on a small number of circadian oscillators resided in many peripheral phase delays showed an intermediate survival genes (Fu and Lee 2003; Hastings et al. tissues of vertebrates and invertebrates (68%). These profound effects of phase shift- 2003). Lesions of the SCN abolish these (Balsalobre et al. 1998; Plautz et al. 1997). ing were not observed in younger mice. The rhythms. Such
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