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Boivin, D. B., Duffy, J. F., Kronauer, R. E., & Czeisler, C. A. (1996). Dose-response relationships for resetting of human circadian clock by light. Nature, 379(6565), 540–542.
Abstract: Since the first report in unicells, studies across diverse species have demonstrated that light is a powerful synchronizer which resets, in an intensity-dependent manner, endogenous circadian pacemakers. Although it is recognized that bright light (approximately 7,000 to 13,000 lux) is an effective circadian synchronizer in humans, it is widely believed that the human circadian pacemaker is insensitive to ordinary indoor illumination (approximately 50-300 lux). It has been proposed that the relationship between the resetting effect of light and its intensity follows a compressive nonlinear function, such that exposure to lower illuminances still exerts a robust effect. We therefore undertook a series of experiments which support this hypothesis and report here that light of even relatively low intensity (approximately 180 lux) significantly phase-shifts the human circadian pacemaker. Our results clearly demonstrate that humans are much more sensitive to light than initially suspected and support the conclusion that they are not qualitatively different from other mammals in their mechanism of circadian entrainment.
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Brainard, G. C., Sliney, D., Hanifin, J. P., Glickman, G., Byrne, B., Greeson, J. M., et al. (2008). Sensitivity of the human circadian system to short-wavelength (420-nm) light. J Biol Rhythms, 23(5), 379–386.
Abstract: The circadian and neurobehavioral effects of light are primarily mediated by a retinal ganglion cell photoreceptor in the mammalian eye containing the photopigment melanopsin. Nine action spectrum studies using rodents, monkeys, and humans for these responses indicate peak sensitivities in the blue region of the visible spectrum ranging from 459 to 484 nm, with some disagreement in short-wavelength sensitivity of the spectrum. The aim of this work was to quantify the sensitivity of human volunteers to monochromatic 420-nm light for plasma melatonin suppression. Adult female (n=14) and male (n=12) subjects participated in 2 studies, each employing a within-subjects design. In a fluence-response study, subjects (n=8) were tested with 8 light irradiances at 420 nm ranging over a 4-log unit photon density range of 10(10) to 10(14) photons/cm(2)/sec and 1 dark exposure control night. In the other study, subjects (n=18) completed an experiment comparing melatonin suppression with equal photon doses (1.21 x 10(13) photons/cm(2)/sec) of 420 nm and 460 nm monochromatic light and a dark exposure control night. The first study demonstrated a clear fluence-response relationship between 420-nm light and melatonin suppression (p<0.001) with a half-saturation constant of 2.74 x 10(11) photons/cm(2)/sec. The second study showed that 460-nm light is significantly stronger than 420-nm light for suppressing melatonin (p<0.04). Together, the results clarify the visible short-wavelength sensitivity of the human melatonin suppression action spectrum. This basic physiological finding may be useful for optimizing lighting for therapeutic and other applications.
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Kloog, I., Portnov, B. A., Rennert, H. S., & Haim, A. (2011). Does the modern urbanized sleeping habitat pose a breast cancer risk? Chronobiol Int, 28(1), 76–80.
Abstract: Due to its disruptive effects on circadian rhythms and sleep deprivation at night, shiftworking is currently recognized as a risk factor for breast cancer (BC). As revealed by the present analysis based on a comparative case-control study of 1679 women, exposure to light-at-night (LAN) in the “sleeping habitat” is significantly associated with BC risk (odds ratio [OR] = 1.220, 95% confidence interval [CI] = 1.118-1.311; p < .001), controlling for education, ethnicity, fertility, and alcohol consumption. The novelty of the present research is that, to the best of the authors' knowledge, it is the first study to have identified an unequivocal positive association between bedroom-light intensity and BC risk. Thus, according to the results of the present study, not only should artificial light exposure in the working environment be considered as a potential risk factor for BC, but also LAN in the “sleeping habitat.”
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Lockley, S. W., Brainard, G. C., & Czeisler, C. A. (2003). High sensitivity of the human circadian melatonin rhythm to resetting by short wavelength light. J Clin Endocrinol Metab, 88(9), 4502–4505.
Abstract: The endogenous circadian oscillator in mammals, situated in the suprachiasmatic nuclei, receives environmental photic input from specialized subsets of photoreceptive retinal ganglion cells. The human circadian pacemaker is exquisitely sensitive to ocular light exposure, even in some people who are otherwise totally blind. The magnitude of the resetting response to white light depends on the timing, intensity, duration, number and pattern of exposures. We report here that the circadian resetting response in humans, as measured by the pineal melatonin rhythm, is also wavelength dependent. Exposure to 6.5 h of monochromatic light at 460 nm induces a two-fold greater circadian phase delay than 6.5 h of 555 nm monochromatic light of equal photon density. Similarly, 460 nm monochromatic light causes twice the amount of melatonin suppression compared to 555 nm monochromatic light, and is dependent on the duration of exposure in addition to wavelength. These studies demonstrate that the peak of sensitivity of the human circadian pacemaker to light is blue-shifted relative to the three-cone visual photopic system, the sensitivity of which peaks at approximately 555 nm. Thus photopic lux, the standard unit of illuminance, is inappropriate when quantifying the photic drive required to reset the human circadian pacemaker.
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Pauley, S. M. (2004). Lighting for the human circadian clock: recent research indicates that lighting has become a public health issue. Med Hypotheses, 63(4), 588–596.
Abstract: The hypothesis that the suppression of melatonin (MLT) by exposure to light at night (LAN) may be one reason for the higher rates of breast and colorectal cancers in the developed world deserves more attention. The literature supports raising this subject for awareness as a growing public health issue. Evidence now exists that indirectly links exposures to LAN to human breast and colorectal cancers in shift workers. The hypothesis begs an even larger question: has medical science overlooked the suppression of MLT by LAN as a contributor to the overall incidence of cancer? The indirect linkage of breast cancer to LAN is further supported by laboratory rat experiments by David E. Blask and colleagues. Experiments involved the implanting of human MCF-7 breast cancer cell xenografts into the groins of rats and measurements were made of cancer cell growth rates, the uptake of linoleic acid (LA), and MLT levels. One group of implanted rats were placed in light-dark (12L:12D) and a second group in light-light (12L:12L) environments. Constant light suppressed MLT, increased cancer cell growth rates, and increased LA uptake into cancer cells. The opposite was seen in the light-dark group. The proposed mechanism is the suppression of nocturnal MLT by exposure to LAN and subsequent lack of protection by MLT on cancer cell receptor sites which allows the uptake of LA which in turn enhances the growth of cancer cells. MLT is a protective, oncostatic hormone and strong antioxidant having evolved in all plants and animals over the millennia. In vertebrates, MLT is normally produced by the pineal gland during the early morning hours of darkness, even in nocturnal animals, and is suppressed by exposure to LAN. Daily entrainment of the human circadian clock is important for good human health. These studies suggest that the proper use and color of indoor and outdoor lighting is important to the health of both humans and ecosystems. Lighting fixtures should be designed to minimize interference with normal circadian rhythms in plants and animals. New discoveries on blue-light-sensitive retinal ganglion cell light receptors that control the circadian clock and how those receptors relate to today's modern high intensity discharge (HID) lamps are discussed. There is a brief discussion of circadian rhythms and light pollution. With the precautionary principle in mind, practical suggestions are offered for better indoor and outdoor lighting practices designed to safeguard human health.
Keywords: Human Health; Chronobiology Disorders/*complications/*physiopathology; Circadian Rhythm/*radiation effects; Clinical Trials as Topic; Environmental Exposure/adverse effects; Evidence-Based Medicine; Humans; Light; Lighting/*adverse effects/methods; Melatonin/metabolism; *Models, Biological; Neoplasms/*etiology/*physiopathology; Occupational Diseases/etiology/physiopathology; Public Health/methods/trends; Risk Assessment/methods; Risk Factors
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