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Author Phillips, A.J.K.; Vidafar, P.; Burns, A.C.; McGlashan, E.M.; Anderson, C.; Rajaratnam, S.M.W.; Lockley, S.W.; Cain, S.W.
Title High sensitivity and interindividual variability in the response of the human circadian system to evening light Type Journal Article
Year 2019 Publication Proceedings of the National Academy of Sciences of the United States of America Abbreviated Journal Proc Natl Acad Sci U S A
Volume 116 Issue 24 Pages 12019-12024
Keywords Human Health; circadian rhythms; light sensitivity; circadian disruption; melatonin suppression; evening light
Abstract Before the invention of electric lighting, humans were primarily exposed to intense (>300 lux) or dim (<30 lux) environmental light-stimuli at extreme ends of the circadian system's dose-response curve to light. Today, humans spend hours per day exposed to intermediate light intensities (30-300 lux), particularly in the evening. Interindividual differences in sensitivity to evening light in this intensity range could therefore represent a source of vulnerability to circadian disruption by modern lighting. We characterized individual-level dose-response curves to light-induced melatonin suppression using a within-subjects protocol. Fifty-five participants (aged 18-30) were exposed to a dim control (<1 lux) and a range of experimental light levels (10-2,000 lux for 5 h) in the evening. Melatonin suppression was determined for each light level, and the effective dose for 50% suppression (ED50) was computed at individual and group levels. The group-level fitted ED50 was 24.60 lux, indicating that the circadian system is highly sensitive to evening light at typical indoor levels. Light intensities of 10, 30, and 50 lux resulted in later apparent melatonin onsets by 22, 77, and 109 min, respectively. Individual-level ED50 values ranged by over an order of magnitude (6 lux in the most sensitive individual, 350 lux in the least sensitive individual), with a 26% coefficient of variation. These findings demonstrate that the same evening-light environment is registered by the circadian system very differently between individuals. This interindividual variability may be an important factor for determining the circadian clock's role in human health and disease.
Address (down) Turner Institute for Brain and Mental Health, School of Psychological Sciences, Monash University, Melbourne, Victoria, Australia sean.cain@monash.edu
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 0027-8424 ISBN Medium
Area Expedition Conference
Notes PMID:31138694 Approved no
Call Number IDA @ intern @ Serial 2521
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Author Anbalagan, M.; Dauchy, R.; Xiang, S.; Robling, A.; Blask, D.; Rowan, B.; Hill, S.
Title SAT-337 Disruption Of The Circadian Melatonin Signal By Dim Light At Night Promotes Bone-lytic Breast Cancer Metastases Type Journal Article
Year 2019 Publication Journal of the Endocrine Society Abbreviated Journal
Volume 3 Issue Supplement_1 Pages
Keywords Human Health; Cancer; Breast cancer; melatonin; shift work; mouse models
Abstract Breast cancer metastasis to bone is a major source of morbidity and mortality in women with advanced metastatic breast cancer. Morbidity from metastasis to bone is compounded by the fact that they cannot be surgically removed and can only be treated with chemotherapy and/or radiation therapy. Thus, there is critical need to develop new treatment strategies that kill bone metastatic tumors and reduce osteolytic lesions to improve patient quality of life and extend patient survival. Circadian rhythms are daily cycles of ~24 h that control many if not most physiologic processes and their disruption by exposure to light at night (LAN) or jet lag has been shown to be strongly associated with the development of cancer, particularly breast cancer. We have found that disruption of the anti-cancer circadian hormone melatonin (MLT) by light at night can significantly enhance the metastatic potential in breast cancer cells. Our work supports the report of the International Agency for Research on Cancer that shift work is a “probable human carcinogen” and highlights the association between exposure to light at night and invasive breast cancer. We recently reported that human breast tumor xenografts grown in athymic nude female rats housed in a photoperiod of 12h light at day: 12h dim light at night (dLAN, 0.2 lux – blocks the nighttime circadian MLT signal), display resistance to doxorubicin (Dox). More importantly, tumor growth and drug resistance could be blocked by the administration of Dox in circadian alignment with nocturnal MLT during dLAN. Our recent preliminary studies show that poorly invasive ERα positive MCF-7 breast cancer cells, when injected into the tibia (to mimic bone metastatic disease) of Foxn1nu athymic nude mice (which produce a strong circadian nighttime melatonin signal) housed in a dLAN photoperiod (suppressed nocturnal MLT production) developed full blown breast cancer tumors in bone (P<0.05) that are highly osteolytic (P<0.05). Moreover, patients with metastatic breast cancer are routinely treated with doxorubicin, which itself can promote bone damage. Our studies demonstrate that MLT slows the growth of metastatic breast cancer in bone but that the chrono-therapeutic use of doxorubicin in circadian alignment with melatonin in Foxn1nu mice with tibial breast tumors, reduced tumor growth in bone, reduced bone erosion, and promoted the formation of new bone. Successful use of this chronotherapeutic use of Dox and MLT in clinical trials increasing efficacy in preventing or suppressing breast cancer metastasis to bone while decreasing toxic side effects of doxorubicin would provide a revolutionary advancement in the treatment of bone metastatic breast cancer and decrease the morbidity and mortality associated with breast cancer metastasis to bone.
Address (down) Tulane University School of Medicine, New Orleans, LA, United States
Corporate Author Thesis
Publisher Oxford Academic Place of Publication Editor
Language English Summary Language English Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 2472-1972 ISBN Medium
Area Expedition Conference
Notes Approved no
Call Number GFZ @ kyba @ Serial 2433
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Author Xiang, S.; Dauchy, R.T.; Hoffman, A.E.; Pointer, D.; Frasch, T.; Blask, D.E.; Hill, S.M.
Title Epigenetic inhibition of the tumor suppressor ARHI by light at night-induced circadian melatonin disruption mediates STAT3-driven paclitaxel resistance in breast cancer Type Journal Article
Year 2019 Publication Journal of Pineal Research Abbreviated Journal J Pineal Res
Volume 67 Issue 2 Pages e12586
Keywords Animals; Human Health; Circadian Rhythm; Cancer; tumor suppression
Abstract Disruption of circadian time structure and suppression of circadian nocturnal melatonin (MLT) production by exposure to dim light at night (dLAN), as occurs with night shift work and/or disturbed sleep-wake cycles, is associated with a significantly increased risk of breast cancer and resistance to tamoxifen and doxorubicin. Melatonin inhibition of human breast cancer chemo-resistance involves mechanisms including suppression of tumor metabolism and inhibition of kinases and transcription factors which are often activated in drug-resistant breast cancer. Signal Transducer and Activator of Transcription 3 (STAT3), frequently overexpressed and activated in Paclitaxel (PTX)-resistant breast cancer, promotes the expression of DNA methyltransferase one (DNMT1) to epigenetically suppresses the transcription of tumor suppressor Aplasia Ras homolog one (ARHI) which can sequester STAT3 in the cytoplasm to block PTX-resistance. We demonstrate that breast tumor xenografts in rats exposed to dLAN and circadian MLT disrupted express elevated levels of phosphorylated and acetylated STAT3, increased DNMT1, but reduced Sirtuin 1 (SIRT1) and ARHI. Furthermore, MLT and/or SIRT1 administration blocked/reversed Interleukin 6 (IL-6)-induced acetylation of STAT3 and its methylation of ARH1 to increase ARH1 mRNA expression in MCF-7 breast cancer cells. Finally, analyses of the I-SPY 1 trial demonstrates that elevated MT1 receptor expression is significantly correlated with pathologic complete response following neo-adjuvant therapy in breast cancer patients. This is the first study to demonstrate circadian disruption of MLT by dLAN driving intrinsic resistance to PTX via epigenetic mechanisms increasing STAT3 expression and that MLT administration can reestablish sensitivity of breast tumors to PTX and drive tumor regression.
Address (down) Tulane Circadian Cancer Biology Group, New Orleans, Louisiana
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 0742-3098 ISBN Medium
Area Expedition Conference
Notes PMID:31077613 Approved no
Call Number GFZ @ kyba @ Serial 2383
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Author Bapary, M.A.J.; Takano, J.-I.; Soma, S.; Sankai, T.
Title Effect of blue LED light and antioxidants potential in a somatic cell Type Journal Article
Year 2019 Publication Cell Biology International Abbreviated Journal Cell Biol Int
Volume 43 Issue 11 Pages 1296-1306
Keywords Cells; Biology; LED; blue light; Antioxidants; cell death
Abstract Light is an indispensable part of routine laboratory works in which conventional light is generally used. Light-emitting diodes (LEDs) have come to replace the conventional light thus could be a potent target in biomedical studies. Since blue light is a major component of visible light wavelength, in this study, using a somatic cell from African green monkey kidney, we assessed the possible consequences of blue spectra of LED light in future animal experiments and proposed a potent mitigation against light induced damages. COS-7 cells were exposed to blue LED light (450 nm) and the growth and DNA damage were assessed at different exposure times. A higher suppression in cell growth and viability was observed under a longer period of blue LED light exposure. The number of apoptotic cells increased as light exposure time was prolonged. Reactive oxygen species generation was also elevated in accordance to the extension of light exposure times. A comparison to dark-maintained cells revealed that the upregulation of ROS by blue LED light plays a significant role in causing cellular dysfunction in DNA in a time-dependent manner. In turn, antioxidant treatment has shown to improve the cell growth and viability under blue LED light conditions. This indicates that antioxidants are potential against blue LED light-induced somatic cell damage. It is expected that this study will contribute to the understanding of the basic mechanism of somatic cell death under visible light and to maximize the beneficial use of LED light in future animal experiments.
Address (down) Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan
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 1065-6995 ISBN Medium
Area Expedition Conference
Notes PMID:30958611 Approved no
Call Number GFZ @ kyba @ Serial 2328
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Author Spitschan, M.; Cajochen, C.
Title Binocular facilitation in light-mediated melatonin suppression? Type Journal Article
Year 2019 Publication Journal of Pineal Research Abbreviated Journal J Pineal Res
Volume 67 Issue 4 Pages e12602
Keywords Human Health; Vision; melatonin suppression; monocular; binocular
Abstract Astronomers and pilots have known for a long time that closing one eye can preserve vision in that eye while going from dark to light and back. Recently, it was reported that viewing a smartphone monocularly in an otherwise dark room can lead to transient, but strong reductions in retinal sensitivity in that eye (Alim-Marvasti, Bi, Mahroo, Barbur, & Plant, 2016). But seeing detail is not the only function that is mediated by the retina. Here, we address the question whether light exposure to one eye only (monocular) has tangible effects on the suppression of melatonin by light, relative to both eyes open (binocular).
Address (down) Transfaculty Research Platform Molecular and Cognitive Neurosciences, University of Basel, Basel, Switzerland
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 0742-3098 ISBN Medium
Area Expedition Conference
Notes PMID:31361918 Approved no
Call Number GFZ @ kyba @ Serial 2595
Permanent link to this record