Artificial light-at-night – a novel lifestyle risk factor for metabolic disorder and cancer morbidity (original) (raw)
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Artificial light at night: melatonin as a mediator between the environment and epigenome
Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2015
The adverse effects of excessive use of artificial light at night (ALAN) are becoming increasingly evident and associated with several health problems including cancer. Results of epidemiological studies revealed that the increase in breast cancer incidents co-distribute with ALAN worldwide. There is compiling evidence that suggests that melatonin suppression is linked to ALAN-induced cancer risks, but the specific genetic mechanism linking environmental exposure and the development of disease is not well known. Here we propose a possible genetic link between environmental exposure and tumorigenesis processes. We discuss evidence related to the relationship between epigenetic remodelling and oncogene expression. In breast cancer, enhanced global hypomethylation is expected in oncogenes, whereas in tumour suppressor genes local hypermethylation is recognized in the promoter CpG chains. A putative mechanism of action involving epigenetic modifications mediated by pineal melatonin is d...
Chronobiology International, 2019
Currently, one of the most disputed hypotheses regarding breast cancer (BC) development is exposure to short wavelength artificial light at night (ALAN) as multiple studies suggest a possible link between them. This link is suggested to be mediated by nocturnal melatonin suppression that plays an integral role in circadian regulations including cell division. The objective of the research was to evaluate effects of 1 × 30 min/midnight ALAN (134 µ Wcm −2 , 460 nm) with or without nocturnal melatonin supplement on tumor development and epigenetic responses in 4T1 tumorbearing BALB/c mice. Mice were monitored for body mass (W b) and tumor volume for 3 weeks and thereafter urine samples were collected at regular intervals for determining daily rhythms of 6-sulfatoxymelatonin (6-SMT). Finally, mice were sacrificed and the tumor, lungs, liver, and spleen were excised for analyzing the total activity of DNA methyltransferases (DNMT) and global DNA methylation (GDM) levels. Mice exposed to ALAN significantly reduced 6-SMT levels and increased W b , tumor volume, and lung metastasis compared with controls. These effects were diminished by melatonin. The DNMT activity and GDM levels showed tissue-specific response. The enzymatic activity and GDM levels were lower in tumor and liver and higher in spleen and lungs under ALAN compared with controls. Our results suggest that ALAN disrupts the melatonin rhythm and potentially leading to increased BC burden by affecting DNMT activity and GDM levels. These data may also be applicable to early detection and management of BC by monitoring melatonin and GDM levels as early biomarker of ALAN circadian disruption.
Epigenetics [Working Title]
Epigenetics is an important tool for understanding the relation between environmental exposures and cellular functions, including metabolic and proliferative responses. At our research center, we have devolved a mouse model for characterizing the relation between exposure to artificial light at night (ALAN) and both global DNA methylation (GDM) and breast cancer. Generally, the model describes a close association between ALAN and cancer responses. Cancer responses are eminent at all light spectra, with the prevalent manifestation at the shorter end of the visible spectrum. ALAN-induced pineal melatonin suppression is the principal candidate mechanism mediating the environmental exposure at the molecular level by eliciting aberrant GDM modifications. The carcinogenic potential of ALAN can be ameliorated in mice by exogenous melatonin treatment. In contrast to BALB/c mice, humans are diurnal species, and thus, it is of great interest to evaluate the ALAN-melatonin-GDM nexus also in a diurnal mouse model. The fat sand rat (Psammomys obesus) provides an appropriate model as its responses to photoperiod are comparable to humans. Interestingly, melatonin and thyroxin have opposite effects on GDM levels in P. obesus. Melatonin, GDM levels, and even thyroxin may be utilized as novel biomarkers for detection, staging, therapy, and prevention of breast cancer progression.
Light-Mediated Perturbations of Circadian Timing and Cancer Risk: A Mechanistic Analysis
Integrative Cancer Therapies, 2009
In industrialized countries, certain types of cancer, most notably, breast and prostate, are more frequent than in poorly developed nations. This high cancer frequency is not explained by any of the conventional causes. Within the past decade, numerous reports have appeared that link light at night with an elevated cancer risk. The three major consequences of light at night are sleep deprivation, chronodisruption, and melatonin suppression. Each of these individually or in combination may contribute to the reported rise in certain types of cancer. In this article, the potential mechanisms underlying the basis of the elevated cancer risk are briefly discussed. Finally, if cancer is a consequence of excessive nighttime light, it is likely that other diseases/conditions may also be exaggerated by the widespread use of light after darkness onset.
Carcinogenic effects of circadian disruption: an epigenetic viewpoint
Circadian rhythms refer to the endogenous rhythms that are generated to synchronize physiology and behavior with 24-h environmental cues. These rhythms are regulated by both external cues and molecular clock mechanisms in almost all cells. Disruption of circadian rhythms, which is called circadian disruption, affects many biological processes within the body and results in different long-term diseases, including cancer. Circadian regulatory pathways result in rhythmic epigenetic modifications and the formation of circadian epigenomes. Aberrant epigenetic modifications, such as hypermethylation, due to circadian disruption may be involved in the transformation of normal cells into cancer cells. Several studies have indicated an epigenetic basis for the carcinogenic effects of circadian disruption. In this review, I first discuss some of the circadian genes and regulatory proteins. Then, I summarize the current evidence related to the epigenetic modifications that result in circadian disruption. In addition, I explain the carcinogenic effects of circadian disruption and highlight its potential role in different human cancers using an epigenetic viewpoint. Finally, the importance of chronotherapy in cancer treatment is highlighted.
Light-at-Night-Induced Circadian Disruption, Cancer and Aging
Current Aging Science, 2013
Light-at-night has become an increasing and essential part of the modem lifestyle and leads to a number of health problems, including excessive body mass index, cardiovascular diseases, diabetes, and cancer. The International Agency for Research on Cancer (IARC) Working Group concluded that "shift-work that involves circadian disruption is probably carcinogenic to humans" (Group 2A) [1]. According to the circadian disruption hypothesis, light-at-night might disrupt the endogenous circadian rhythm and specifically suppress nocturnal production of the pineal hormone melatonin and its secretion into the blood. We evaluated the effect of various light/dark regimens on the survival, life span, and spontaneous and chemical carcinogenesis in rodents. Exposure to constant illumination was followed by accelerated aging and enhanced spontaneous tumorigenesis in female CBA and transgenic HER-2/neu mice. In male and female rats maintained at various light/dark regimens (standard 12:12 light/dark [LD] , the natural light [NL] of northwestern Russia, constant light [LL] , and constant darkness [DD]) from the age of25 days until natural death, it was found that exposure to NL and LL regimens accelerated age-related switch-off of the estrous function (in females) , induced development of metabolic syndrome and spontaneous tumorigenesis, and shortened life span both in male and females rats compared to the standard LD regimen. Melatonin given in nocturnal drinking water prevented the adverse effect of the constant illumination (LL) and natural light (NL) regimens on the homeostasis, life span, and tumor development both in mice and rats. The exposure to the LL regimen accelerated colon carcinogenesis induced by 1 ,2-dimethylhydrazine (DMH) in rats, whereas the treatment with melatonin alleviated the effects of LL. The maintenance of rats at the DD regimen inhibited DMH-induced carcinogenesis. The LL regimen accelerated, whereas the DD regimen inhibited both mammary carcinogenesis induced by N-nitrosomethylurea and transplacental carcinogenesis induced by N-nitrosoethylurea in rats. Treatment with melatonin prevented premature aging and tumorigenesis in rodents. The data found in the literature and our observations suggest that the use of melatonin would be effective for cancer prevention in humans at risk as a result of light pollution.
Journal of Local and Global Health Science, 2013
Incidents of non-communicable diseases (NCD) like cardiovascular diseases, cancer, diabetes, and chronic respiratory disease have increased dramatically and are currently the leading causes of death worldwide. Their rising incidents coincide with the dramatic changes in industrialization and development of societies over the past few hundred years. Therefore, current lifestyle practices should be further explored to uncover novel risk factors for certain cancers (i.e. colon, prostate, and breast cancer), metabolic syndrome (i.e. diabetes and obesity), and cardiovascular disease (i.e. coronary artery disease). This review discusses how a disruption of the "biological clock" or circadian rhythms could be involved in the development of these diseases as circadian rhythms control multiple physiological processes such as wake/sleep cycles, hormonal levels, body temperature, metabolism, and immune system.
Mechanisms by which circadian rhythm disruption may lead to cancer
South African Journal of Science, 2010
Humans have evolved in a rhythmic environment and display daily (circadian) rhythms in physiology, metabolism and behaviour that are in synchrony with the solar day. Modern lifestyles have compromised the exposure to bright light during the day and dark nights, resulting in the desynchronisation of endogenously generated circadian rhythms from the external environment and loss of coordination between rhythms within the body. This has detrimental effects on physical and mental health, due to the misregulation and uncoupling of important cellular and physiological processes. Long-term shift workers who are exposed to bright light at night experience the greatest disruption of their circadian rhythms. Studies have shown an association between exposure to light at night, circadian rhythm disruption and an increased risk of cancer. Previous reviews have explored the relevance of light and melatonin in cancer, but here we explore the correlation of circadian rhythm disruption and cancer in terms of molecular mechanisms affecting circadian gene expression and melatonin secretion.
2015
In an attempt to reduce Carbon Dioxide production, lighting technologies are aiming toward the developing of energetically efficient illumination sources as light-emitting diodes (LEDs). LED lamps emit light at shortwavelengths close to the sensitivity peak of melatonin suppression and expected to further exacerbate circadian disruption and cancer risk from increasing exposure to artificial light-at-night (ALAN). We report the effect of ALAN (1×30 min per night) emitted from yellow incandescent or blue-white LED bulbs and melatonin treatment on urinary 6-sulfatoxymelatonin (6-SMT), tumor growth (volume and mass), and global DNA methylation in 4T1 inoculated Balb/c female mice. Blue ALAN significantly decreased 6-SMT, increased tumor growths, and promoted metastasis formation verses yellow exposure. In blue-treated mice, DNA methylation levels were decreased in tumor and liver cells but not in lung and spleen cells compared with yellow-treated mice. Melatonin treatment inhibited tumo...