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Author (up) Agbaria, S.; Haim, A.; Fares, F.; Zubidat, A.E. url  doi
openurl 
  Title Epigenetic modification in 4T1 mouse breast cancer model by artificial light at night and melatonin – the role of DNA-methyltransferase Type Journal Article
  Year 2019 Publication Chronobiology International Abbreviated Journal Chronobiol Int  
  Volume 36 Issue 5 Pages 629-643  
  Keywords Animals  
  Abstract 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 x 30 min/midnight ALAN (134 micro Wcm(-2), 460 nm) with or without nocturnal melatonin supplement on tumor development and epigenetic responses in 4T1 tumor-bearing BALB/c mice. Mice were monitored for body mass (Wb) 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 Wb, 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.  
  Address b The Israeli Center for Interdisciplinary Research in Chronobiology , University of Haifa, Haifa , Israel; Zubidat3(at)013.net.il  
  Corporate Author Thesis  
  Publisher Taylor & Francis Place of Publication Editor  
  Language English Summary Language English Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0742-0528 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:30746962 Approved no  
  Call Number IDA @ john @ Serial 2211  
Permanent link to this record
 

 
Author (up) Asher, A.; Shabtay, A.; Brosh, A.; Eitam, H.; Agmon, R.; Cohen-Zinder, M.; Zubidat, A.E.; Haim, A. url  doi
openurl 
  Title “Chrono-functional milk”: The difference between melatonin concentrations in night-milk versus day-milk under different night illumination conditions Type Journal Article
  Year 2015 Publication Chronobiology International Abbreviated Journal Chronobiol Int  
  Volume 32 Issue 10 Pages 1409-1416  
  Keywords Animals; Heart rate; illumination; melatonin; night-milk; chronobiology  
  Abstract Pineal melatonin (MLT) is produced at highest levels during the night, under dark conditions. We evaluated differences in MLT-concentration by comparing daytime versus night time milk samples, from two dairy farms with different night illumination conditions: (1) natural dark (Dark-Night); (2) short wavelength Artificial Light at Night (ALAN, Night-Illuminated). Samples were collected from 14 Israeli Holstein cows from each commercial dairy farm at 04:30 h (“Night-milk”) 12:30 h (“Day-milk”) and analyzed for MLT-concentration. In order to study the effects of night illumination conditions on cows circadian rhythms, Heart Rate (HR) daily rhythms were recorded. MLT-concentrations of Night-milk samples from the dark-night group were significantly (p < 0.001) higher than those of Night-illuminated conditions (30.70 +/- 1.79 and 17.81 +/- 0.33 pg/ml, respectively). Interestingly, night illumination conditions also affected melatonin concentrations at daytime where under Dark-Night conditions values are significantly (p < 0.001) higher than Night-Illuminated conditions, (5.36 +/- 0.33 and 3.30 +/- 0.18 pg/ml, respectively). There were no significant differences between the two treatments in the milk yield and milk composition except somatic cell count (SCC), which was significantly lower (p = 0.02) in the Dark-Night group compared with the Night-Illuminated group. Cows in both groups presented a significant (p < 0.01) HR daily rhythm, therefore we assume that in the night illuminated cows feeding and milking time are the “time keeper”, while in the Dark-night cows, HR rhythms were entrained by the light/dark cycle. The higher MLT-concentration in Dark-night cows with the lower SCC values calls upon farmers to avoid exposure of cows to ALAN. Therefore, under Dark-night conditions milk quality will improve by lowering SCC values where separation between night and day of such milk can produce chrono-functional milk, naturally rich with MLT.  
  Address b Department of Evolutionary and Environmental Biology , Faculty of Natural Sciences, The Israeli Center for Interdisciplinary Research in Chronobiology, University of Haifa , Mount Carmel , Haifa , Israel  
  Corporate Author Thesis  
  Publisher Taylor & Francis Place of Publication Editor  
  Language English Summary Language English Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0742-0528 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:26588495 Approved no  
  Call Number IDA @ john @ Serial 1312  
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Author (up) Grubisic, M.; Haim, A.; Bhusal, P.; Dominoni, D.M.; Gabriel, K.M.A.; Jechow, A.; Kupprat, F.; Lerner, A.; Marchant, P.; Riley, W.; Stebelova, K.; van Grunsven, R.H.A.; Zeman, M.; Zubidat, A.E.; Hölker, F. url  doi
openurl 
  Title Light Pollution, Circadian Photoreception, and Melatonin in Vertebrates Type Journal Article
  Year 2019 Publication Sustainability Abbreviated Journal Sustainability  
  Volume 11 Issue 22 Pages 6400  
  Keywords Animals; Review  
  Abstract Artificial light at night (ALAN) is increasing exponentially worldwide, accelerated by the transition to new efficient lighting technologies. However, ALAN and resulting light pollution can cause unintended physiological consequences. In vertebrates, production of melatonin—the “hormone of darkness” and a key player in circadian regulation—can be suppressed by ALAN. In this paper, we provide an overview of research on melatonin and ALAN in vertebrates. We discuss how ALAN disrupts natural photic environments, its effect on melatonin and circadian rhythms, and different photoreceptor systems across vertebrate taxa. We then present the results of a systematic review in which we identified studies on melatonin under typical light-polluted conditions in fishes, amphibians, reptiles, birds, and mammals, including humans. Melatonin is suppressed by extremely low light intensities in many vertebrates, ranging from 0.01–0.03 lx for fishes and rodents to 6 lx for sensitive humans. Even lower, wavelength-dependent intensities are implied by some studies and require rigorous testing in ecological contexts. In many studies, melatonin suppression occurs at the minimum light levels tested, and, in better-studied groups, melatonin suppression is reported to occur at lower light levels. We identify major research gaps and conclude that, for most groups, crucial information is lacking. No studies were identified for amphibians and reptiles and long-term impacts of low-level ALAN exposure are unknown. Given the high sensitivity of vertebrate melatonin production to ALAN and the paucity of available information, it is crucial to research impacts of ALAN further in order to inform effective mitigation strategies for human health and the wellbeing and fitness of vertebrates in natural ecosystems.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 2071-1050 ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number GFZ @ kyba @ Serial 2733  
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Author (up) Haim, A.; Zubidat, A.E. url  doi
openurl 
  Title Artificial light at night: melatonin as a mediator between the environment and epigenome Type Journal Article
  Year 2015 Publication Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences Abbreviated Journal Philos Trans R Soc Lond B Biol Sci  
  Volume 370 Issue Pages 20140121  
  Keywords Human Health; melatonin; epigenetic modifications; epigenetics; epigenome; light pollution; breast cancer; oncogenesis; tumorigenesis; biomarkers  
  Abstract 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 discussed in relation to cancer prevalence. Taking into account that ALAN-induced epigenetic modifications are reversible, early detection of cancer development is of great significance in the treatment of the disease. Therefore, new biomarkers for circadian disruption need to be developed to prevent ALAN damage.  
  Address The Israeli Center for Interdisciplinary Research in Chronobiology, Department of Evolutionary and Environmental Biology, University of Haifa, Mount Carmel, Haifa 31905, Israel; ahaim@research.haifa.ac.il  
  Corporate Author Thesis  
  Publisher Royal Society Place of Publication Editor  
  Language English Summary Language English Original Title  
  Series Editor Series Title The biological impacts of artificial light at night: from molecules to communities Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN ISBN Medium  
  Area Expedition Conference  
  Notes Approved no  
  Call Number IDA @ john @ Serial 1119  
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Author (up) Zubidat, A.E.; Fares, B.; Fares, F.; Haim, A. url  doi
openurl 
  Title Artificial Light at Night of Different Spectral Compositions Differentially Affects Tumor Growth in Mice: Interaction With Melatonin and Epigenetic Pathways Type Journal Article
  Year 2018 Publication Cancer Control : Journal of the Moffitt Cancer Center Abbreviated Journal Cancer Control  
  Volume 25 Issue 1 Pages 1073274818812908  
  Keywords Human Health; 6-Smt; Cfl; EE-halogen; GDM-levels; body mass; carbon; corticosterone; cosinor analysis; light at night; yellow-LED  
  Abstract Lighting technology is rapidly advancing toward shorter wavelength illuminations that offer energy-efficient properties. Along with this advantage, the increased use of such illuminations also poses some health challenges, particularly breast cancer progression. Here, we evaluated the effects of artificial light at night (ALAN) of 4 different spectral compositions (500-595 nm) at 350 Lux on melatonin suppression by measuring its urine metabolite 6-sulfatoxymelatonin, global DNA methylation, tumor growth, metastases formation, and urinary corticosterone levels in 4T1 breast cancer cell-inoculated female BALB/c mice. The results revealed an inverse dose-dependent relationship between wavelength and melatonin suppression. Short wavelength increased tumor growth, promoted lung metastases formation, and advanced DNA hypomethylation, while long wavelength lessened these effects. Melatonin treatment counteracted these effects and resulted in reduced cancer burden. The wavelength suppression threshold for melatonin-induced tumor growth was 500 nm. These results suggest that short wavelength increases cancer burden by inducing aberrant DNA methylation mediated by the suppression of melatonin. Additionally, melatonin suppression and global DNA methylation are suggested as promising biomarkers for early diagnosis and therapy of breast cancer. Finally, ALAN may manifest other physiological responses such as stress responses that may challenge the survival fitness of the animal under natural environments.  
  Address 1 The Israeli Center for Interdisciplinary Research in Chronobiology, University of Haifa, Haifa, Israel  
  Corporate Author Thesis  
  Publisher SAGE Place of Publication Editor  
  Language English Summary Language English Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1073-2748 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:30477310; PMCID:PMC6259078 Approved no  
  Call Number IDA @ john @ Serial 2143  
Permanent link to this record
 

 
Author (up) Zubidat, A.E.; Haim, A. url  doi
openurl 
  Title Artificial light-at-night – a novel lifestyle risk factor for metabolic disorder and cancer morbidity Type Journal Article
  Year 2017 Publication Journal of Basic and Clinical Physiology and Pharmacology Abbreviated Journal J Basic Clin Physiol Pharmacol  
  Volume 28 Issue 4 Pages 295-313  
  Keywords Human Health  
  Abstract Both obesity and breast cancer are already recognized worldwide as the most common syndromes in our modern society. Currently, there is accumulating evidence from epidemiological and experimental studies suggesting that these syndromes are closely associated with circadian disruption. It has been suggested that melatonin (MLT) and the circadian clock genes both play an important role in the development of these syndromes. However, we still poorly understand the molecular mechanism underlying the association between circadian disruption and the modern health syndromes. One promising candidate is epigenetic modifications of various genes, including clock genes, circadian-related genes, oncogenes, and metabolic genes. DNA methylation is the most prominent epigenetic signaling tool for gene expression regulation induced by environmental exposures, such as artificial light-at-night (ALAN). In this review, we first provide an overview on the molecular feedback loops that generate the circadian regulation and how circadian disruption by ALAN can impose adverse impacts on public health, particularly metabolic disorders and breast cancer development. We then focus on the relation between ALAN-induced circadian disruption and both global DNA methylation and specific loci methylation in relation to obesity and breast cancer morbidities. DNA hypo-methylation and DNA hyper-methylation, are suggested as the most studied epigenetic tools for the activation and silencing of genes that regulate metabolic and monostatic responses. Finally, we discuss the potential clinical and therapeutic roles of MLT suppression and DNA methylation patterns as novel biomarkers for the early detection of metabolic disorders and breast cancer development.  
  Address  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 0792-6855 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:28682785 Approved no  
  Call Number LoNNe @ kyba @ Serial 1680  
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