Of Mice and Women: Light as a Circadian Stimulus in Breast Cancer Research

ObjectiveNocturnal rodents are frequently used as models in human breast cancer research, but these species have very different visual and circadian systems and, therefore, very different responses to optical radiation or, informally, light. Because of the impact of light on the circadian system and because recent evidence suggests that cancer risk might be related to circadian disruption, it is becoming increasingly clear that optical radiation must be properly characterized for both nocturnal rodents and diurnal humans to make significant progress in unraveling links between circadian disruption and breast cancer. In this paper, we propose a quantitative framework for comparing radiometric and photometric quantities in human and rodent studies.MethodsWe reviewed published research on light as a circadian stimulus for humans and rodents. Both suppression of nocturnal melatonin and phase shifting were examined as outcome measures for the circadian system.ResultsThe data were used to develop quantitative comparisons regarding the absolute and spectral sensitivity for the circadian systems of humans and nocturnal rodents.ConclusionsTwo models of circadian phototransduction, for mouse and humans, have been published providing spectral sensitivities for these two species. Despite some methodological variations among the studies reviewed, the circadian systems of nocturnal rodents are approximately 10,000 times more sensitive to optical radiation than that of humans. Circadian effectiveness of different sources for both humans and nocturnal rodents are offered together with a scale relating their absolute sensitivities. Instruments calibrated in terms of conventional photometric units (e.g., lux) will not accurately characterize the circadian stimulus for either humans or rodents.

[1]  R. Foster,et al.  Regulation of the mammalian pineal by non-rod, non-cone, ocular photoreceptors. , 1999, Science.

[2]  Anders Eklund,et al.  Background light adaptation of the retinal neuronal adaptive system , 2001, Documenta Ophthalmologica.

[3]  G. Brainard,et al.  Ultraviolet regulation of neuroendocrine and circadian physiology in rodents , 1994, Vision Research.

[4]  R. Stevens,et al.  Night shift work, light at night, and risk of breast cancer. , 2001, Journal of the National Cancer Institute.

[5]  D. Skene,et al.  An action spectrum for melatonin suppression: evidence for a novel non‐rod, non‐cone photoreceptor system in humans , 2001, The Journal of physiology.

[6]  B. Asselain,et al.  Familial Breast Cancer: Clinical Response to Induction Chemotherapy or Radiotherapy Related to BRCA1/2 Mutations Status , 2009, American journal of clinical oncology.

[7]  G. Brainard,et al.  Suppression of pineal melatonin in Peromyscus leucopus by different monochromatic wavelengths of visible and near-ultraviolet light (UV-A) , 1987, Brain Research.

[8]  John D. Bullough,et al.  Phototransduction for human melatonin suppression , 2002, Journal of pineal research.

[9]  R. Reiter,et al.  Photoreceptor damage and eye pigmentation: influence on the sensitivity of rat pineal N-acetyltransferase activity and melatonin levels to light at night. , 1985, Neuroendocrinology.

[10]  Cohen Bb,et al.  Familial breast cancer. , 1992, Seminars in Cancer Biology.

[11]  H. Wright,et al.  Differential effects of light wavelength in phase advancing the melatonin rhythm , 2004, Journal of pineal research.

[12]  Z. Boulos.  Wavelength dependence of light-induced phase shifts and period changes in hamsters , 1995, Physiology & Behavior.

[13]  W. Jongmans,et al.  Cellular responses to radiation and risk of breast cancer. , 1999, European journal of cancer.

[14]  G. Brainard,et al.  The influence of different light spectra on the suppression of pineal melatonin content in the syrian hamster , 1984, Brain Research.

[15]  Charles A Czeisler,et al.  High sensitivity of the human circadian melatonin rhythm to resetting by short wavelength light. , 2003, The Journal of clinical endocrinology and metabolism.

[16]  M. Singaravel,et al.  Relationship between light intensity and phase resetting in a mammalian circadian system. , 1999, The Journal of experimental zoology.

[17]  Green light evokes maximum phase shifts in the locomotor activity rhythm of the field mouse Mus booduga. , 1996, Journal of photochemistry and photobiology. B, Biology.

[18]  R. Foster,et al.  Circadian rhythms in mice can be regulated by photoreceptors with cone-like characteristics , 1995, Brain Research.

[19]  Richard E. Kronauer,et al.  Dose-response relationships for resetting of human circadian clock by light , 1996, Nature.

[20]  P. Riley.  THE MELATONIN HYPOTHESIS: BREAST CANCER AND USE OF ELECTRIC POWER , 1998 .

[21]  R. Reiter,et al.  The influence of different light irradiances on pineal N-acetyltransferase activity and melatonin levels in the cotton rat, Sigmodon hispidus. , 1983, Life sciences.

[22]  R. Foster,et al.  Regulation of mammalian circadian behavior by non-rod, non-cone, ocular photoreceptors. , 1999, Science.

[23]  G. Brainard,et al.  The suppression of nocturnal pineal melatonin in the Syrian hamster: dose-response curves at 500 and 360 nm. , 1987, Endocrinology.

[24]  A. Swerdlow.  Shift work and breast cancer : a critical review of the epidemiological evidence , 2003 .

[25]  T. Williams,et al.  The role of ocular pigmentation in protecting against retinal light damage , 1980, Vision Research.

[26]  J. Takahashi,et al.  Comparison of visual sensitivity for suppression of pineal melatonin and circadian phase-shifting in the golden hamster , 1991, Brain Research.

[27]  Ahmedin Jemal,et al.  Trends in Breast Cancer by Race and Ethnicity , 2003, CA: a cancer journal for clinicians.

[28]  John D. Bullough,et al.  Human melatonin suppression by light: a case for scotopic efficiency , 2001, Neuroscience Letters.

[29]  Richard G. Stevens,et al.  Circadian Disruption and Breast Cancer: From Melatonin to Clock Genes , 2005, Epidemiology.

[30]  S. Amir,et al.  Ultraviolet light entrains rodent suprachiasmatic nucleus pacemaker , 1995, Neuroscience.

[31]  F Laden,et al.  Rotating night shifts and risk of breast cancer in women participating in the nurses' health study. , 2001, Journal of the National Cancer Institute.

[32]  R. Wurtman,et al.  Control of the rat pineal gland by light spectra. , 1972, Proceedings of the National Academy of Sciences of the United States of America.

[33]  Francis Lévi,et al.  Disruption of circadian coordination accelerates malignant growth in mice. , 2003, Pathologie-biologie.

[34]  R. Stevens,et al.  Electric power use and breast cancer: a hypothesis. , 1987, American journal of epidemiology.

[35]  R. Wurtman,et al.  Light intensities required to suppress nocturnal melatonin secretion in albino and pigmented rats. , 1984, Life sciences.

[36]  W. Hrushesky.  Circadian timing of cancer chemotherapy. , 1985, Science.

[37]  Rea,et al.  Lighting Handbook: Reference & Application , 1993 .

[38]  B A Miller,et al.  Recent trends in U.S. breast cancer incidence, survival, and mortality rates. , 1996, Journal of the National Cancer Institute.

[39]  G. Brainard,et al.  Action Spectrum for Melatonin Regulation in Humans: Evidence for a Novel Circadian Photoreceptor , 2001, The Journal of Neuroscience.

[40]  Francis Lévi,et al.  Host circadian clock as a control point in tumor progression. , 2002, Journal of the National Cancer Institute.

[41]  R. Reiter,et al.  Differential response of pineal melatonin levels to light at night in laboratory-raised and wild-captured 13-lined ground squirrels (Spermophilus tridecemlineatus). , 1983, Life sciences.

[42]  R. Stevens.  Circadian Disruption and Breast Cancer , 2005 .

[43]  S. M. Pauley.  Lighting for the human circadian clock: recent research indicates that lighting has become a public health issue. , 2004, Medical hypotheses.

[44]  R. Reiter,et al.  Non-suppressibility by room light of pineal N-acetyltransferase activity and melatonin levels in two diurnally active rodents, the Mexican ground squirrel (Spermophilus mexicanus) and the eastern chipmunk (Tamias striatus). , 1984, Endocrine research.

[45]  R. Stevens,et al.  The melatonin hypothesis: electric power and breast cancer. , 1996, Environmental health perspectives.

[46]  Iain M McIntyre,et al.  Human Melatonin Suppression by Light is Intensity Dependent , 1989, Journal of pineal research.

[47]  W. Rand,et al.  Entrainment of the Body Temperature Rhythm in Rats: Effect of Color and Intensity of Environmental Light , 1973, Science.

[48]  J. Hansen,et al.  Light at night, shiftwork, and breast cancer risk. , 2001, Journal of the National Cancer Institute.

[49]  M. Lévesque.  Perception , 1986, The Yale Journal of Biology and Medicine.

[50]  Susan E Hankinson,et al.  Urinary melatonin levels and breast cancer risk. , 2005, Journal of the National Cancer Institute.

[51]  Patricia Wood,et al.  Circadian Timing in Cancer Treatment: The Biological Foundation for an Integrative Approach , 2003, Integrative cancer therapies.

[52]  MS Rea,et al.  Circadian photobiology: an emerging framework for lighting practice and research , 2002 .

[53]  L. Fu,et al.  The circadian clock: pacemaker and tumour suppressor , 2003, Nature Reviews Cancer.

[54]  John D. Bullough,et al.  Evaluating light source efficacy under mesopic conditions using reaction times , 1997 .

[55]  G. Brainard,et al.  The effect of different light intensities on pineal melatonin content , 1982, Brain Research.

[56]  David E. Blask,et al.  Growth and Fatty Acid Metabolism of Human Breast Cancer (MCF-7) Xenografts in Nude Rats: Impact of Constant Light-Induced Nocturnal Melatonin Suppression , 2003, Breast Cancer Research and Treatment.

[57]  Iain M McIntyre,et al.  Quantal melatonin suppression by exposure to low intensity light in man. , 1989, Life sciences.

[58]  John D. Bullough,et al.  A model of phototransduction by the human circadian system , 2005, Brain Research Reviews.

[59]  T. Yoshimura,et al.  Spectral sensitivity of photoreceptors mediating phase-shifts of circadian rhythms in retinally degenerate CBA/J (rd/rd) and normal CBA/N (+/+) mice , 1996, Journal of Comparative Physiology A.

[60]  L. Goldstein,et al.  Prognostic and predictive factors in early-stage breast cancer. , 2004, The oncologist.

[61]  Mark S. Rea,et al.  Light in the Built Environment: Potential role of Circadian Disruption in Endocrine Disruption and Breast Cancer , 2001, Cancer Causes & Control.

[62]  John D. Bullough,et al.  Additivity in Murine Circadian Phototransduction , 2005, Zoological science.

[63]  Edward N. Pugh,et al.  From candelas to photoisomerizations in the mouse eye by rhodopsin bleaching in situ and the light-rearing dependence of the major components of the mouse ERG , 2004, Vision Research.

[64]  D A Newsome,et al.  Light suppresses melatonin secretion in humans. , 1980, Science.

[65]  John D. Bullough,et al.  Preliminary evidence for spectral opponency in the suppression of melatonin by light in humans , 2004, Neuroreport.

[66]  H. Wright,et al.  EFFECT OF LIGHT WAVELENGTH ON SUPPRESSION AND PHASE DELAY OF THE MELATONIN RHYTHM , 2001, Chronobiology international.

[67]  G. Brainard,et al.  Dim light during darkness stimulates tumor progression by enhancing tumor fatty acid uptake and metabolism. , 1999, Cancer letters.

[68]  Mark S. Rea,et al.  The Daysimeter: a device for measuring optical radiation as a stimulus for the human circadian system , 2005 .

[69]  R. A. Wiseman.  Breast cancer: critical data analysis concludes that estrogens are not the cause, however lifestyle changes can alter risk rapidly. , 2004, Journal of clinical epidemiology.

[70]  Debra J. Skene,et al.  Phase advancing human circadian rhythms with short wavelength light , 2003, Neuroscience Letters.

[71]  G. Brainard,et al.  Influence of light irradiance on hydroxyindole-O-methyltransferase activity, serotonin-N-acetyltranferase activity, and radioimmunoassayable melatonin levels in the pineal gland of the diurnally active Richardson's ground squirrel , 1983, Brain Research.

[72]  J. Takahashi,et al.  Spectral sensitivity of a novel photoreceptive system mediating entrainment of mammalian circadian rhythms , 1984, Nature.

[73]  Josephine Arendt,et al.  Short-Wavelength Sensitivity of the Human Circadian System to Phase-Advancing Light , 2005, Journal of biological rhythms.

[74]  R. Reiter.  Action Spectra, Dose‐Response Relationships, and Temporal Aspects of Light's Effects on the Pineal Gland , 1985, Annals of the New York Academy of Sciences.

[75]  R. Kronauer,et al.  Sensitivity of the human circadian pacemaker to nocturnal light: melatonin phase resetting and suppression , 2000, The Journal of physiology.