Light At Night Exposure Research Articles

Outdoor Light at Night and Diabetes Incidence in the Danish Nurse Cohort Study

Background/Aim: Recent animal studies suggested that light-at-night (LAN) may impair glucose tolerance in rats and disturb glucose homeostasis. We aimed to evaluate the association between exposure to residential outdoor LAN and diabetes incidence in Denmark. Methods: In the nationwide Danish Nurse Cohort consisting of 23,797 nurses, recruited in 1993 or 1999, we identified 1,065 diabetes incident cases through National Diabetes Register up to 2012. The LAN data was estimated using Global Radiance Calibrated products of the Defense Meteorological Satellite Program (DMSP) for 1996, 1999, 2000, 2002, 2004, 2005, and 2010. The full residential address histories were obtained and the LAN exposure was assigned based on the 1996 data for addresses before 1997, and based on the most recent measure for addresses after 1997. Time-varying Cox regression models were used to estimate hazard ratios (HR) (95% confidence intervals (CI)) for the associations of LAN and diabetes incidence, adjusting for individual anthropometric, lifestyle and environmental covariates, such as residential air pollution (PM2.5 and NO2), and night-time road traffic noise determined by validated models. Results: The estimated HR based on a fully adjusted model for incident diabetes with an interquartile range (IQR) (75.6 nW/cm2/sr) increase in cumulative average outdoor LAN was 1.13 (95% CI: 1.05, 1.21). Based on the fully adjusted model of LAN exposure divided into quintiles, where LAN quintile 1 was reference, we found an increase in diabetes incidence at higher LAN levels: LAN quintile 2: HR: 1.04 (95% CI: 0.86-1.27, p = 0.66), LAN quintile 3: HR: 1.04 (95% CI: 0.85-1.26, p = 0.71), LAN quintile 4: HR: 0.99 (0.81-1.20, p = 0.91), and LAN quintile 5: HR: 1.21 (95% CI: 1.0-1.46, p = 0.053). Conclusion: We found suggestive evidence that outdoor LAN exposure may be associated with diabetes incidence, independent of air pollution and road traffic noise.

Outdoor Light at Night and Breast Cancer Incidence in the Danish Nurse Cohort Study

Introduction: Breast cancer is the most common cancer type, and the most common reason for cancer-related deaths among women worldwide. Animal and epidemiologic studies suggest that exposure to light at night may contribute to increased breast cancer risk through circadian disruption, which involves a decrease in the nocturnal secretion of melatonin followed by disturbed estrogen regulation, however, epidemiological evidence is limited. In this study, we examined the association between exposure to residential outdoor light at night (LAN) and breast cancer incidence in the Danish Nurse Cohort Study. Methods: We followed 20,404 Danish nurses from 1993 or 1999 through 2012. LAN exposure was estimated using the US Defense Meteorological Satellite Program's (DMSP) Operational Linescan System. We collected LAN data (nW/cm2/sr) for 1996, 1999, 2000, 2002, 2004, 2005, and 2010, assigned at the subject's residence during the follow-up. Data on the incidence of breast cancer was obtained from the Danish Cancer Registry. We used time-varying Cox regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for reproductive, lifestyle and environmental factors such as residential air pollution, road traffic noise, and greenspace. Results: Of the 20,490 women, 1,081 developed breast cancer in total during 339,633 person-years of follow-up. Based on the fully adjusted model of LAN exposure divided into quintiles, where the lowest LAN quintile was reference (0-13.6 nW/cm2/sr), we found an increase in breast cancer incidence at higher LAN levels: HR: 1.01 (95% CI: 0.83-1.23, p = 0.92), 1.08 (95% CI: 0.88-1.33, p = 0.44), 1.04 (0.83-1.30, p = 0.74), and 0.87 (95% CI: 0.66-1.15, p = 0.32) for the 2nd, 3rd, 4th, and 5th quintiles, respectively. Conclusion: There was a tendency, that higher levels of exposure to LAN were associated with a higher risk of breast cancer although the statistical significance was not observed.

Light at night exposure and cancer: A cancer hazard evaluation

Background: Modern electric lighting practices have transformed our society into one in which people work, sleep, and receive goods and services 24/7. As the light-dark cycle is the major stimulus for coordinating the circadian system, exposure to light at night (LAN) can lead to circadian disruption (CD) and potential adverse health effects.Methods: The U.S. National Toxicology Program (NTP) conducted a cancer hazard evaluation of exposure to LAN that included a systematic review of epidemiology studies of female breast cancer. The human studies assessed LAN exposure in the sleeping area (i.e., “indoor light”) or from outdoor light, mostly by using satellite imaging methods (e.g., “environmental LAN”). We characterized all identified studies as low or moderate quality based on our bias and sensitivity evaluation.Results and discussion: The 10 studies of indoor LAN provided inconsistent findings due to heterogeneity in methods used to measure LAN levels and the lack of specificity regarding LAN levels. Cohort or case-control studies of environmental LAN consistently found an increased risk of breast cancer among women in the highest category of overall LAN or blue-light LAN exposure. Whether these measurements provide a relevant direct measure of light or are surrogates for other activities enabled by light is not clear. Furthermore, whether low light levels observed in these studies are sufficient to disrupt circadian rhythms remains a question. NTP concluded the epidemiological database was inadequate to evaluate the relationship between exposure to LAN and female breast cancer.Conclusions: Mechanistic and toxicological data studies provide strong evidence that certain lighting conditions (excessive LAN and insufficient daylight) can cause CD, biological effects characteristic of carcinogens, and promote breast or mammary tumor growth, thus providing moderate confidence of carcinogenicity in humans. Additional studies precisely measuring exposure to all sources of LAN and characterizing LAN intensities and spectral characteristics are needed.

Association Between Outdoor Light at Night and Risk of Coronary Heart Disease among 60,229 Older Adults: A Prospective Cohort Study

Background Light at night (LAN) is the most important environmental cue for circadian misalignment, which may increase risk of coronary heart disease through impairing circadian rhythms. We aimed to estimate the association between exposure to outdoor LAN and coronary heart disease (CHD) in elders.MethodsWe followed 60,229 Hong Kong elders free of CHD from 1998 through 2011. Annual LAN exposure was estimated using time-varying satellite data for a composite of persistent nighttime illumination at ~1 km2 scale for each residence. We used Cox proportional hazard models to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between exposure to outdoor LAN and risk of CHD. Results Over 10 to 13 years of follow-up, we identified 3,772 incident CHD cases and 1,695 CHD deaths. Annual levels of LAN at participants’ residential addresses ranged from 2.2 to 233.1 nW/cm2/sr. The concentration-response functions for the association between LAN and CHD incidence and mortality were approximate linear with the slopes becoming flat when LAN above 110 nW/cm2/sr. Per interquartile range (IQR) (60.0 nW/cm2/sr) increase in outdoor LAN, the HR was 1.09 (95% CI: 1.03, 1.17) for CHD incidence and 1.10 (95% CI: 1.01, 1.22) for CHD mortality after adjusting for both individual and area-level risk factors.Conclusions Exposure to outdoor light at night was associated with higher risk of coronary heart disease among Hong Kong elders. Our findings highlight the need to regulate light pollution for the potential coronary heart disease benefits.

Assessing the relationship between outdoor light at night (using International Space Station photographs) and risk of breast cancer in Vancouver, British Columbia

Background/Aim: Chronobiological and epidemiologic studies suggest that exposure to light at night (LAN) disrupts circadian rhythms, which in turn may increase breast cancer risk. The aim of this study is to investigate how different spectral parameters of outdoor LAN, as measured by the International Space Station (ISS), are associated with breast cancer risk, particularly in terms of the blue part of the spectrum. Methods: A population-based case-control study was conducted in Vancouver, BC, Canada with incident breast cancer cases and controls frequency matched by age. This analysis was restricted to 687 cases and 719 controls who provided lifetime residential histories. Using time-weighted average duration at each home 5-20 years prior to study entry, measures of cumulative average outdoor LAN exposure were estimated using ISS photographs, with a total of six LAN measures of intensity and varying spectra. Outdoor LAN measures were categorized into tertiles, and logistic regression was used to estimate the associations between outdoor LAN and breast cancer risk and potential interactions by menopausal status and night shift work. Results: Most participants lived at one or two residences during the 5-20 year time period of interest prior to study enrolment (median of two residences, maximum of eight residences). Preliminary results do not suggest an association between the various spectral LAN measures and breast cancer risk, and there is no clear interaction by menopausal status or past/current night work status. Conclusions: Our preliminary findings are consistent with no relationship between spectra and intensity of outdoor LAN measured using ISS photographs of Vancouver and risk of breast cancer. Strengths include the use of images with higher resolution around residences, and analysis of outdoor LAN using various biologically relevant parameters. More work is needed to understand the specific mechanisms linking LAN to breast cancer risk, particularly in terms of blue light exposure.

Exposure to light at night (LAN) and risk of breast cancer: A systematic review and meta-analysis

BackgroundWith the unprecedented urbanization light pollution has emerged as a ubiquitous problem, and there has been accumulating evidence on the links between exposure to light at night (LAN) and breast cancer risk. We conducted a systematic review and meta-analysis of published studies on the associations between LAN exposure and breast cancer risk. MethodsWe included all observational human studies wherein the exposure variable was LAN measured in indoor and outdoor environments, and the outcome was breast cancer. We employed summary relative risks (SRR) for breast cancer by comparing highest versus lowest categories of LAN exposure within a random-effects model. The National Toxicology Program's (NTP) Office of Health Assessment and Translation (OHAT) risk of bias rating tool was adopted to assess the risk of bias in individual studies and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guideline was employed to assess confidence in the body of evidence. ResultsA total 14 studies comprising four cohorts (13,155 cases among 372,802 exposed subjects), nine case-control and one case-referent studies of female subjects (39,462 cases and 20,739 controls) across seven countries and published between 2001 and 20 were included for review. Participants in the highest LAN exposure category were associated with higher risk of breast cancer in reference to those in the lowest (SRR: 1.12; 95% CI: 1.06–1.18; I2 = 39% for outdoor LAN, and SRR: 1.13; 95%CI: 1.05–1.21; I2 = 19% for indoor LAN). Pooled evidence identified relatively pronounced association of outdoor LAN exposure and breast cancer among women with estrogen receptor positive (ER+) tumor (SRR: 1.21; 95% CI: 1.04–1.40) and premenopausal status (SRR: 1.21; 95% CI: 1.06–1.37). The final rate of confidence in the body of evidence generated was graded as ‘moderate’ based on GRADE guideline. DiscussionLAN exposure was consistently associated with higher breast cancer risk corroborating NTP's recommendations which anticipates excessive LAN as human carcinogen.

A large prospective investigation of outdoor light at night and obesity in the NIH-AARP Diet and Health Study

BackgroundResearch has suggested that artificial light at night (LAN) may disrupt circadian rhythms, sleep, and contribute to the development of obesity. However, almost all previous studies are cross-sectional, thus, there is a need for prospective investigations of the association between LAN and obesity risk. The goal of our current study was to examine the association between baseline LAN and the development of obesity over follow-up in a large cohort of American adults.MethodsThe study included a sample of 239,781 men and women (aged 50–71) from the NIH-AARP Diet and Health Study who were not obese at baseline (1995–1996). We used multiple logistic regression to examine whether LAN at baseline was associated with the odds of developing obesity at follow-up (2004–2006). Outdoor LAN exposure was estimated from satellite imagery and obesity was measured based on self-reported weight and height.ResultsWe found that higher outdoor LAN at baseline was associated with higher odds of developing obesity over 10 years. Compared with the lowest quintile of LAN, the highest quintile was associated with 12% and 19% higher odds of developing obesity at follow-up in men (OR (95% CI) = 1.12 (1.00, 1.250)) and women (1.19 (1.04, 1.36)), respectively.ConclusionsOur findings suggest that high LAN exposure could predict a higher risk of developing obesity in middle-to-older aged American adults.

Metabolic Implications of Exposure to Light at Night: Lessons from Animal and Human Studies.

Lately, the incidence of overweight, obesity, and type 2 diabetes has shown a staggering increase. To prevent and treat these conditions, one must look at their etiology. As life on earth has evolved under the conditions of nature’s 24‐hour light/dark cycle, it seems likely that exposure to artificial light at night (LAN) would affect physiology. Indeed, ample evidence has shown that LAN impacts many metabolic parameters, at least partly via the biological clock in the suprachiasmatic nucleus of the hypothalamus. This review focuses on the impact of chronic and acute effects of LAN of different wavelengths on locomotor activity, food intake, the sleep/wake cycle, body temperature, melatonin, glucocorticoids, and glucose and lipid metabolism. While chronic LAN disturbs daily rhythms in these parameters, experiments using short‐term LAN exposure also have shown acute negative effects in metabolically active peripheral tissues. Experiments using LAN of different wavelengths not only have indicated an important role for melanopsin, the photopigment found in intrinsically photosensitive retinal ganglion cells, but also provided evidence that each wavelength may have a specific impact on energy metabolism. Importantly, exposure to LAN has been shown to impact glucose homeostasis also in humans and to be associated with an increased incidence of overweight, obesity, and atherosclerosis.

Outdoor light at night and postmenopausal breast cancer risk in the NIH-AARP diet and health study.

Circadian disruption may play a role in breast carcinogenesis. Previous studies reported relationships between outdoor light at night (LAN) and the breast cancer risk, but their findings are mixed. There is also a need to examine LAN and breast cancer incidence according to different individual and environmental characteristics to identify subpopulations at greater risk associated with LAN exposure. We studied residential outdoor LAN estimated from satellite imagery at baseline (1996) in relation to postmenopausal breast cancer incidence over ~16 years of follow-up in 186 981 postmenopausal women including 12 318 incident postmenopausal breast cancer cases in the NIH-AARP Diet and Health Study. We used Cox proportional hazards models to estimate hazard ratios (HR) and two-sided 95% confidence intervals (CI) of the relationship between quintiles of LAN and postmenopausal breast cancer risk, overall and by hormone receptor status and cancer stage. We found that when compared to women in the lowest quintile of baseline LAN, those in the highest quintile had a 10% increase in postmenopausal breast cancer risk (HR (95% CI), 1.10 (1.02, 1.18), P-trend, .002). The association appeared to be stronger for estrogen receptor (ER) positive breast cancer (1.12 [1.02, 1.24], .007) than for ER-negative cancer (1.07 [0.85, 1.34], .66). Our findings also suggested that the relationship between LAN and breast cancer risk may differ by individual characteristics, such as smoking, alcohol drinking, sleep duration and BMI, and neighborhood environment. In conclusion, our study suggests that higher outdoor LAN exposure may be a risk factor for postmenopausal breast cancer.

Models of modern-day circadian rhythm disruption and their diabetogenic potentials in adult male Wistar rats

Background: Light at night (LAN) threatens metabolic health by delaying our sleep timing and allowing us to eat at odds with our circadian clocks. Circadian research interests are majorly focused on jet lags, shift work, and the non-24-h days. Since exposure to LAN, sleep loss, and late night eating are common scenarios of modern-day circadian rhythm disruption, developing an animal model that better mirrors these scenarios and investigation of their diabetogenic potentials is a research priority. Materials and Methods: Over the course of 6 weeks, we developed chronic LAN exposure (LAN), sleep restriction (SR), abnormal feeding (AF), rural social jetlag (RSJ), night shift work (NSW), and urban social jetlag (USJ) models, using male Wistar rats. Gentle handling was used to induce SR, while LAN was instituted using a customized light rack system. Circadian and blood glucose rhythms were, respectively, determined using 4 hourly temperature and blood glucose measurements. Statistical analysis was done using SPSS V20.0 and OCosinor SoftwareO. The data were summarized using mean ± standard deviation as well as MESoRs, amplitudes, and acrophases. Statistical significance was considered as P ≤ 0.05. Results: Our findings have revealed a significantly (P < 0.01) higher average nocturnal glucose (126 mg/dL) and temperature (36.53°C) rhythms compared to diurnal glucose (108 mg/dL) and temperature (35.50°C) rhythms in the controls rats. All the developed models are noted to have a distorted light: dark glucose and temperature rhythms with acrophases of the core body temperature in controls, RSJ and USJ models occurring at 08:16 pm, 2:43 pm, and 7:48 pm local time, respectively. The vector components of the phase changes revealed 5 h phase delay in the LAN model and 28 min, 1 h, and 4.5 h phase advancements among the USJ, AF, and SR models, respectively. These indicate circadian disruption and blood glucose dysrhythmia among the SR, AF, LAN, RSJ, USJ, and NSW models. Conclusion: Our findings have suggested the circadian disruptive and diabetogenic nature of our widespread modern-day social behaviors.

Light exposure patterns and sleep in children

OPS 27: Radiation, EMF and morbidity, Room 210, Floor 2, August 27, 2019, 10:30 AM - 12:00 PM Background: Experimental studies have reported effects of evening or light at night (LAN) exposure on melatonin and sleep. Few studies have been performed in children that objectively assessed light exposure and sleep under normal living conditions. We aimed at exploring effects of timing of first instance of, and duration (in minutes) of bright daylight exposure (>1000lux), light in the hour before children went to bed, and bedroom LAN exposure on sleep onset delay, sleep efficiency and sleep duration in 244 children aged 11-13 years. Methods: Children were instructed to wear a light meter (logging average illuminance per 10 seconds) as a pendant during the day, to place it on their nightstand during the night, and to wear an accelerometer on their non-dominant wrist during 8 days (logging interval 100Hz). We evaluated the effect of light metrics on sleep efficiency and sleep onset delay (both dichotomized at the 80th percentile) using mixed effects logistic regression, and on sleep duration using linear mixed models, nested in participants and adjusted for age, sex and weekday. Results: We observed reduced sleep efficiency and longer sleep onset delay in children with higher light levels in the hour before they went to bed, but not with LAN levels or with the duration of bright light children had received during the day. In contrast, LAN levels and duration of bright light during the day, but not light in the hour before children went to bed, were associated with shorter sleep duration. Timing of bright light did not affect assessed sleep outcomes. Interpretation: Exposure to light received at different time points during the day, evening or night has effects on different aspects of sleep.

Light exposure at night and sleep quality in bipolar disorder: The APPLE cohort study

BackgroundSleep disturbance in bipolar disorder (BD) is common and is associated with a risk for mood episode recurrence. Thus, it is important to identify factors that are related to sleep disturbance in BD. This cross-sectional study investigated the association between exposure to light at night (LAN) and sleep parameters in patients with BD. MethodsThe sleep parameters of 175 outpatients with BD were recorded using actigraphy at their homes for seven consecutive nights and were evaluated using the Insomnia Severity Index (ISI). The average LAN intensity in the bedroom during bedtime and rising time was measured using a portable photometer, and the participants were divided into two groups: “Light” (≥5 lx) and “Dark” (<5 lx). The association between LAN and sleep parameters was tested with multivariable analysis by adjusting for potential confounder such as age, gender, current smoker, mood state, day length, daytime light exposure, and sedative medications. ResultsAfter adjusting for potential confounder, the actigraphy sleep parameters showed significantly lower sleep efficiency (mean, 80.1%vs. 83.4%; p = 0.01), longer log-transformed sleep onset latency (2.9 vs. 2.6 min; p = 0.01), and greater wake after sleep onset (51.4 vs. 41.6 min; p = 0.02) in the Light group than in the Dark group. Whereas, there were no significant differences in the ISI scores between the groups. LimitationsThis was a cross-sectional study; therefore, the results do not necessarily imply that LAN causes sleep disturbance. ConclusionsReducing LAN exposure may contribute to improved sleep quality in patients with BD.

Effects of Light-at-Night on the Rat Liver – A Role for the Autonomic Nervous System

Exposure to light at night (LAN) has been associated with serious pathologies, including obesity, diabetes and cancer. Recently we showed that 2 h of LAN impaired glucose tolerance in rats. Several studies have suggested that the autonomic nervous system (ANS) plays an important role in communicating these acute effects of LAN to the periphery. Here, we investigated the acute effects of LAN on the liver transcriptome of male Wistar rats. Expression levels of individual genes were not markedly affected by LAN, nevertheless pathway analysis revealed clustered changes in a number of endocrine pathways. Subsequently, we used selective hepatic denervations [sympathetic (Sx), parasympathetic (Px), total (Tx, i.e., Sx plus Px), sham] to investigate the involvement of the ANS in the effects observed. Surgical removal of the sympathetic or parasympathetic hepatic branches of the ANS resulted in many, but small changes in the liver transcriptome, including a pathway involved with circadian clock regulation, but it clearly separated the four denervation groups. On the other hand, analysis of the liver metabolome was not able to separate the denervation groups, and only 6 out of 78 metabolites were significantly up- or downregulated after denervations. Finally, removal of the sympathetic and parasympathetic hepatic nerves combined with LAN exposure clearly modulated the effects of LAN on the liver transcriptome, but left most endocrine pathways unaffected.Conclusion: One-hour light-at-night acutely affects the liver transcriptome. Part of this effect is mediated via the nervous innervation, as a hepatectomy modulated and reduced the effect of LAN on liver transcripts.

Light at night exacerbates metabolic dysfunction in a polygenic mouse model of type 2 diabetes mellitus

AimsElectric lighting is beneficial to modern society; however, it is becoming apparent that light at night (LAN) is not without biological consequences. Several studies have reported negative effects of LAN on health and behavior in humans and nonhuman animals. Exposure of non-diabetic mice to dim LAN impairs glucose tolerance, whereas a return to dark nights (LD) reverses this impairment. We predicted that exposure to LAN would exacerbate the metabolic abnormalities in TALLYHO/JngJ (TH) mice, a polygenic model of type 2 diabetes mellitus (T2DM). Materials and methodsWe exposed 7-week old male TH mice to either LD or LAN for 8–10 weeks in two separate experiments. After 8 weeks of light treatment, we conducted intraperitoneal glucose tolerance testing (ipGTT) followed by intraperitoneal insulin tolerance testing (ipITT). In Experiment 1, all mice were returned to LD for 4 weeks, and ipITT was repeated. Key findingsThe major results of this study are i) LAN exposure for 8 weeks exacerbates glucose intolerance and insulin resistance ii) the effects of LAN on insulin resistance are reversed upon return to LD, iii) LAN exposure results in a greater increase in body weight compared to LD exposure, iv) LAN increases the incidence of mice developing overt T2DM, and v) LAN exposure decreases survival of mice with T2DM. SignificanceIn conclusion, LAN exacerbated metabolic abnormalities in a polygenic mouse model of T2DM, and these effects were reversed upon return to dark nights. The applicability of these findings to humans with T2DM needs to be determined.

Shedding Some Light in the Dark-A Comparison of Personal Measurements with Satellite-Based Estimates of Exposure to Light at Night among Children in the Netherlands.

Background:Exposure to light at night (LAN) can perturb the biological clock and affect sleep and health. Previous epidemiological studies have evaluated LAN levels measured by satellites, but the validity of this measure as a proxy for personal LAN exposure is unclear. In addition, outdoor satellite-measured LAN levels are higher in urban environments, which means that this measure could potentially represent a proxy for other, likely urban, environmental exposures.Objectives:We evaluated correlations of satellite-assessed LAN with measured bedroom light levels and explored correlations with other environmental exposures, in particular, air pollution, green space, and area-level socioeconomic position (SEP).Methods:We compared satellite measurements with evening and nighttime bedroom measurements of illuminance (in units of lux) for 256 children, and we evaluated correlations between satellite-based measures and other urban exposures such as air pollution, area-level SEP, and surrounding green space for 3,021 children.Results:Satellite-measured LAN levels (nanowatts per centimeter squared per steradian) were not correlated with measured evening or nighttime lux levels [Spearman correlation coefficients () to 0.04]. There was a weak correlation with measurements during the darkest time period if parents and their children reported that outdoor light sometimes or usually influenced indoor light levels (, ). In contrast, satellite-measured LAN levels were correlated with air pollution ( with , with ), and surrounding green space ( for green space within of the home). A weak correlation with area-level SEP was also observed ().Conclusions:Outdoor satellite-assessed outdoor LAN exposure levels were correlated with urban environmental exposures, but they were not a good proxy for indoor evening or nighttime personal exposure as measured in our study population of 12-y-old children. Studies planning to evaluate potential risks from LAN should consider such modifying factors as curtains and indoor lighting and the use of electronic devices and should include performing indoor or personal measurements to validate any exposure proxies. The moderate-to-strong correlation of outdoor LAN with other environmental exposures should be accounted for in epidemiological investigations. https://doi.org/10.1289/EHP3431

Prior exposure to dim light at night impairs dermal wound healing in female C57BL/6 mice.

Artificial light at night (LAN) is a pervasive phenomenon in today's society, and the detrimental consequences of LAN exposure are becoming apparent. LAN is associated with the increased incidence of metabolic disorders, cancers, mood alterations, and immune dysfunction in mammals. Consequently, we examined the effects of dim LAN (DLAN) on wound healing. Female C57BL/6 mice were housed for 3weeks in DLAN or LD conditions prior to wounding. Following wounding, mice were maintained in either their previous light conditions or switched to the opposite lighting conditions for 3weeks. DLAN prior to wounding impaired healing; specifically, mice in DLAN/DLAN had significantly larger wounds on day 8. Additionally, mice in DLAN/LD had significantly larger wounds on days 5, 7, 8, and 9, and increased average time to closure. These data demonstrate a potential harmful effect of DLAN on wound healing that should be considered and may represent a target for therapeutic intervention.

Sex and estrous cycle dependent changes in locomotor activity, anxiety and memory performance in aged mice after exposure of light at night.

Light-at-night (LAN) can affect mammalian behaviour. But, the effects of LAN on aged rodents remain undefined yet. In the present investigation, aged Swiss Albino mice, habituated in regular light-dark cycle, were exposed to bright-light-pulse (1-h) at night on the day of study followed by experimentations for assessment of locomotor activities in the open field, anxiety in the elevated plus maze and short-term memory for novel object recognition (NOR) in the habituated field. Under without-bright-light exposure, (a) aged proestrous females showed greater locomotor activities and less anxiety than in aged diestrous females, (b) aged males showed locomotor activities and anxiety level similar to aged diestrous females and aged proestrous females respectively and (c) all animals failed to retain in object discrimination memory. LAN exposure exhibited the continual failure of such retention of memory while animals showed free and spontaneous exploration with thigmotactic behaviour having no object bias and/or phobia, but time stay in objects by animals altered variably among sexes and stages of estrous cycle. Overall, the LAN caused (a) diminution in locomotor activities, rise in anxiety and failure of memory for recognition of both familiar and novel objects in aged proestrous females, (b) hyperlocomotor activities and reduction in anxiety in both males and diestrous females with the failure of memory for recognition of novel objects only in aged males while diestrous females showed enhanced exploration time to both objects during NOR. Thus, nocturnal behaviour of aged mice varies with sex and estrous cycle and light acts differentially on them.

Shedding Some Light in the Dark - Validity of Using Satellite Measurements to Estimate Light at Night Exposure

Background: Exposure to light at night (LAN) can perturb the biological clock and affect sleep and health. Several epidemiological studies have evaluated LAN levels measured by satellites, but the validity of this measure as a proxy for personal LAN exposure is unclear. Also, outdoor light at night measured by satellites displays higher levels in urban environments, which means that this measure could potentially represent a proxy for other, likely urban, environmental exposures.Objectives: We evaluated correlations of satellite-assessed LAN with measured bedroom light levels, and explored correlations with other environmental exposures, in particular air pollution, green space and area-level socio-economic position.Methods: We compared satellite measurements with nighttime bedroom measurements in illuminance (Lux) in 251 children and additionally evaluated correlations to other urban exposures such as air pollution, area-level socio-economic position and surrounding green in 3021 children.Results: Satellite-measured LAN levels (nanoW/cm2/sr) were not correlated with bedroom-measured Lux (Spearman corr. coeff. -0.02). There was a weak correlation if parents reported influence of outdoor light on indoor light levels (rS&amp;#61;0.31). Satellite-measured LAN levels were correlated to air pollution (rS&amp;#61;0.76 with NO2, rS&amp;#61;0.71 with PM10) surrounding green (rS&amp;#61;-0.68 for green space within 1km of the home), and weakly to area-level socio-economic position (rS&amp;#61;0.24).Conclusions: Our study results indicate that outdoor satellite-assessed LAN levels are not a good proxy for nighttime personal exposure in bedrooms, but rather a proxy for other urban exposures. Studies planning to evaluate potential risks from LAN should therefore consider modifying factors such as curtains and indoor lighting and perform indoor or personal measurements to validate their exposure proxies. Other environmental exposures should be accounted for in epidemiological investigations.

Abstract LB-237: Circadian dysregulation via exposure to light at night alters DNA methylation of cancer-associated genes in murine mammary tissue

Abstract Breast cancer is a leading cause of cancer deaths among women, with an estimated 12.4% of American women diagnosed with this tumor type. Evidence suggests that exogenous disruptors can exert epigenetic changes leading to aberrant gene expression, putatively shifting the balance toward oncogenesis. While chemical pollutant exposure is well-studied, light exposure may exert diverse effects that are often overlooked. Mounting epidemiological evidence suggests that chronic circadian dysregulation is associated with increased breast cancer risk. Exposure to light at night (LAN) via ambient nighttime lighting, digital technology, shiftwork, and trans-meridian travel can alter temporal organization of cellular processes such as cell cycle regulation and tissue proliferation. Previous studies demonstrated that animals exposed to altered light cycles exhibited marked DNA methylation pattern changes, and aberrant DNA methylation is noted across multiple loci in the cancer genome. LAN exposure may thus contribute to the etiology of breast cancer via alteration of the epigenome and subsequent temporal disruption of typical gene expression patterns. We previously found (unpublished data) that mPer2::luc females exposed to 21 days of LAN (18:6 LD) exhibited profound circadian disruption particularly in mammary chain, in comparison to control-exposed (12:12 LD) mice, and that LAN exposure significantly decreased mammary ERα and ERβ expression. We are continuing to explore LAN-induced molecular alterations in the mammary via whole-genome bisulfite sequencing, to determine if inappropriate light exposure is an etiological risk factor of hormone-dependent mammary cancer. Post-pubertal female mice were exposed to LAN or control light cycles for 21d prior to mammary tissue harvest as described above for mPer2::luc knock-in mice. Genomic DNA samples were bisulfite-converted and sequenced, aligned to a bisulfite-converted genome, and analyzed to identify differential DNA methylation, using probes for regulatory regions (-500 to +2000bp), exons, introns, and CpG islands. LAN exposure induced changes in mean methylation of probes across 6.4% of regulatory regions (2044 of 32025), 5.5% of exons (1752 of 32025), 0.03% of introns (577 of 190791), and 1.9% of CpG islands (269 of 13840) individually analyzed and annotated with surrounding or downstream genes (adjusted p&amp;lt;0.05, abs. min. difference of means &amp;gt;5). Significant methylation changes resulting from LAN were noted in multiple genetic loci implicated in cancer, including directional methylation changes intermediate between control and 4T1 breast cancer models across various Hox genes, Hic1, Cdkn1c, and other genes associated with proliferation and oncogenesis, with commensurate changes in gene expression also observed. We are currently working to confirm relative expression of commensurate genes via qRT-PCR. Together, these results point to a potential mechanism by which LAN exposure may initiate cellular dysregulation within mammary tissue. Citation Format: Rebecca E. Veitch, Shay Bracha, Patrick Chappell. Circadian dysregulation via exposure to light at night alters DNA methylation of cancer-associated genes in murine mammary tissue [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-237.

Light at Night Exposure and Breast Cancer Risk: A Matched Case-Control Study in England

Background/Aim: There is evidence that light at night (LAN) is a breast cancer risk factor, with in vitro and in vivo studies showing LAN can interrupt melatonin production, a hormone with oncostatic properties. Epidemiological evidence is limited, but a case-control study in Georgia, United States, using lung cancer controls, found LAN exposure to be associated with an increased risk of breast cancer. We conducted a matched case-control study to establish the association between outdoor LAN exposure and female breast cancer risk in England. Methods: Cancer data were obtained from the Office for National Statistics for years 2001 to 2012. LAN values were obtained from satellite data and assigned to each case/control’s residential postcode centroid (the geographic centre of a collection of approximately 15 adjacent households). Breast cancer cases aged ≥ 15 years were matched to controls by age at diagnosis (in years) and quintile of neighbourhood-level deprivation. The association between LAN and breast cancer was assessed using: i) skin cancer controls, ii) lung cancer controls, and iii) skin, leukaemia, brain/CNS and urinary organs (excluding kidney) cancer controls, using logistic regression, adjusted for year of diagnosis. Results: Our study included 348,561 matched breast cancer cases/skin cancer controls, 163,896 breast cancer cases/lung cancer controls, and 377,495 breast cancer cases/skin, leukaemia, brain, CNS and urinary organ cancer controls. In preliminary analyses, the risk of breast cancer was lower among women exposed to outdoor LAN when using lung cancer controls (Odds ratio in 5th vs 1st LAN quintile 0.90 (95% CI 0.88-0.92), but higher when using skin cancer controls (OR 5th vs 1st LAN quintile 1.41 (95% CI 1.39-1.43). Conclusions: Globally, breast cancer is the most commonly diagnosed cancer and it has the highest mortality rate among women, and any modifiable risk factors (such as LAN) warrant further investigation to assess possible associations.