Licht, Melatonin und innere Krebserkrankungen - Aktuelle Fakten und Forschungsperspektiven

Zusammenfassung

Sichtbares Licht von ausreichender Intensität hemmt die Biosynthese von Melatonin und es gibt zahlreiche experimentelle Hinweise, dass Melatonin vor Krebs schützen kann. Die Verifizierung oder Falsifizierung der Hypothese, dass Kunstlicht - oder sogar das Sonnenlicht selbst - die Melatoninproduktion so unterdrückt, dass es zu mehr oder früheren Krebserkrankungen innerer Organe kommt, ist von Bedeutung für die öffentliche Gesundheit, da aufgrund der Zahl von ubiquitär exponierten Menschen selbst kleine Risikoerhöhungen zu vielen Erkrankungsfällen führen könnten. Aktuelle epidemiologische Studien von Personen, die im Rahmen von Schichtarbeit gegenüber anthropogenem Licht-bei-Nacht exponiert sind, und erste Auswertungen von natürlichen Lichtexperimenten bei blinden Personen und bei Bewohnern der Arktis sind mit der Möglichkeit vereinbar, dass Licht über Melatonin - zumindest hormonabhängige - Krebsentwicklungen beeinflussen kann. Zur systematischen Untersuchung der Wirkung geografisch unterschiedlicher Lichtintensitäten auf die Melatoninproduktion beim Menschen wird eine pan-europäische Studie vorgeschlagen. Weitere epidemiologische Untersuchungen können zum Verständnis der pathophysiologischen Zusammenhänge zwischen Licht, Melatonin und der Biologie des Menschen beitragen.

Abstract

Visible light of sufficient intensity inhibits melatonin biosynthesis and numerous experimental studies suggest that melatonin may protect against cancer. From a public health point of view it is important to verify or falsify the hypothesis that artificial light - or even sunlight itself - suppresses melatonin production sufficiently to increase the risk of developing cancers of internal organs. Since humans are exposed universally, even small risk elevations could lead to numerous cases. Recent epidemiological studies of people exposed to anthropogenic light-at-night in the course of shift work and first evaluations of natural light experiments in blind people and in residents of the Arctic are compatible with the possibility that light can influence - at least hormone- dependent - cancer developments via melatonin. To systematically investigate the effect of geographically different light intensities on melatonin production in man, a pan-European study is suggested. Further epidemiological investigations can contribute to the understanding of the patho-physiological relationships between light, melatonin and human biology.

Schlüsselwörter

Licht - Melatonin - Krebs - Ubiquitäre Exposition - Dosimetrie

Key words

Light - Melatonin - Cancer - Ubiquitous Exposure - Dosimetry

Literatur

• 1 McCord C P, Allen F P. Evidences associating pineal gland function with alterations in pigmentation.  J Exp Zool. 1917;  23 207-224
• 2 Lerner A B, Case J D. Melatonin. Intersociety symposium on new and neglected hormones.  Federation Proceedings. 1960;  19 590-592
• 3 Lewy A J, Wehr T A, Goodwin F K, Newsome D A, Markey S P. Light suppresses melatonin secretion in humans.  Science. 1980;  210 1267-1269
• 4 Reiter R J. Action spectra, dose-response relationships, and temporal aspects of light’s effects on the pineal gland.  Ann N Y Acad Sci. 1985;  453 215-230
• 5 Brainard G C, Hanifin J P, Rollag M D, Greeson J, Byrne B, Glickman G, Gerner E, Sanford B. Human melatonin regulation is not mediated by the three cone photopic visual system.  J Clin Endocrinol Metab. 2001;  86 433-436
• 6 Czeisler C A, Allan J S, Strogatz S H, Ronda J M, Sanchez R, Rios C D, Freitag W O, Richardson G S, Kronauer R E. Bright light resets the human circadian pacemaker independent of the timing of the sleep-wake cycle.  Science. 1986;  233 667-671
• 7 McIntyre I M, Norman T R, Burrows G D, Armstrong S M. Human melatonin suppression by light is intensity dependent.  J Pineal Res. 1989;  6 149-156
• 8 Brainard G C. Signal transduction of light for melatonin regulation in humans. Stevens RG, Wilson BW, Anderson LE The melatonin hypothesis: breast cancer and use of electric power Ohio; Battelle Press Columbus Richland 1997: 267-296
• 9 McIntyre I M, Norman T R, Burrows G D, Armstrong S M. Melatonin supersensitivity to dim light in seasonal affective disorder.  Lancet. 1990;  335 488
• 10 Monteleone P, Esposito G, La R occa A, Maj M. Does bright light suppress nocturnal melatonin secretion more in women than men?.  J Neural Transm Gen Sect. 1995;  102 75-80
• 11 Boivin D B, Duffy J F, Kronauer R E, Czeisler C A. Dose-response relationships for resetting of human circadian clock by light.  Nature. 1996;  379 540-542
• 12 Takahashi J S. Molecular neurobiology and genetics of circadian rhythms in mammals.  Annu Rev Neurosci. 1995;  18 531-553
• 13 Johnson C H, Golden S S. Circadian programs in cyanobacteria: adaptiveness and mechanism.  Annu Rev Microbiol. 1999;  53 389-409
• 14 Steeves T D, King D P, Zhao Y, Sangoram A M, Du F, Bowcock A M, Moore R Y, Takahashi J S. Molecular cloning and characterization of the human CLOCK gene: expression in the suprachiasmatic nuclei.  Genomics. 1999;  57 189-200
• 15 Amir S, Stewart J. Resetting of the circadian clock by a conditioned stimulus.  Nature. 1996;  379 542-545
• 16 Stevens R G. Electric power use and breast cancer: a hypothesis.  Am J Epidemiol. 1987;  125 556-561
• 17 NIEHS/NIH. Editors Portier CJ, Wolfe MS .Assessment of Health Effects from Exposure to Power-Line Frequency Electric and Magnetic Fields - Working Group Report. EMFRAPID Program/LCBRA, NIEHS, NIH, PO Box 12233, MD A3 - 06; Research Triangle Park, NC 27709 1998 NIH Publication No. 98 - 3981
• 18 Blask D E. Melatonin in oncology. Yu HS, Reiter RJ Melatonin: Biosynthesis, Physiological effects, and Clinical Applications Boca Raton; CRC Press 1993: 447-475
• 19 Tamarkin L, Cohen M, Roselle D, Reichert C, Lippman M, Chabner B. Melatonin inhibition and pinealectomy enhancement of 7,12-dimethylbenz(a)anthracene-induced mammary tumors in the rat.  Cancer Res. 1981;  41 4432-4436
• 20 Blask D E, Pelletier D B, Hill S M, Lemus-Wilson A, Grosso D S, Wilson S T, Wise M E. Pineal melatonin inhibition of tumor promotion in the N-nitroso-N-methylurea model of mammary carcinogenesis: potenzial involvement of antiestrogenic mechanisms in vivo.  J Cancer Res Clin Oncol. 1991;  117 526-532 (6)
• 21 Stevens R G. Biologically based epidemiological studies of electric power and cancer.  Environ Health Perspect. 1993;  101 93-100 (Suppl 4)
• 22 Baldwin W S, Barrett J C. Melatonin: receptor-mediated events that may affect breast and other steroid hormone-dependent cancers.  Mol Carcinog. 1998;  21 149-155
• 23 Hill S M, Teplitzky S, Ram P T, Kiefer T, Blask D E, Spriggs L L, Eck K M. Melatonin synergizes with retinoic acid in the prevention and regression of breast cancer.  Adv Exp Med Biol. 1999;  460 345-362
• 24 Reiter R J, Tan D X, Cabrera J, D’Arpa D. Melatonin and tryptophan derivatives as free radical scavengers and antioxidants.  Adv Exp Med Biol. 1999;  467 379-387
• 25 Cologne Symposium 2000. „Low frequency EMF, Visible Light, Melatonin and Cancer”; International symposium; May 4-5, 2000, University of Cologne,. Erren TC, Piekarski C Zbl Arbeitsmed http://www.uni-koeln.de/symposium2000 15.4.2002 2000 50: 298-314
• 26 Portier C. Decisions about Environmental Health Risks: What are the Key Questions and How Does This Apply to Melatonin? In: Cologne Symposium 2000. „Low frequency EMF, Visible Light, Melatonin and Cancer”; International symposium; May 4-5, 2000; University of Cologne. Erren TC, Piekarski C Zbl Arbeitsmed http://www.uni-koeln.de/symposium2000 15.4.2002 2000 50: 298-314.
• 27 Erren T C. A meta-analysis of epidemiologic studies of electric and magnetic fields and breast cancer in women and men.  Bioelectromagnetics. 2001;  Suppl 5 S105-S119
• 28 Stevens, RG, Davis, S, Thomas, DB, Anderson, LE, Wilson, BW. Electric power, pineal function, and the risk of breast cancer.  FASEB J. 1992;  6 853-860
• 29 Stevens R G, Rea M S. Light in the built environment: potenzial role of circadian disruption in endocrine disruption and breast cancer.  Cancer Causes & Control. 2001;  12 279-287
• 30 Hahn R A. Profound bilateral blindness and the incidence of breast cancer.  Epidemiology. 1991;  2 208-210
• 31 Erren T C, Piekarski C. Does winter darkness in the Artic protect against cancer? The melatonin hypothesis revisited.  Med Hypotheses. 1999;  53 1-5
• 32 Erren T C, Bjerregaard P, Cocco P, Lerchl A, Verkasalo P K. EMF dosimetry by geography - beyond black box epidemiology. Re: „Invited commentary: electromagnetic fields and cancer in railway workers”.  Am J Epidemiol. 2001;  154 977-979
• 33 Pukkala E, Auvinen A, Wahlberg G. Incidence of cancer among Finnish airline cabin attendants, 1967-92.  BMJ. 1995;  311 649-652
• 34 Tynes T, Hannevik M, Andersen A, Vistnes A I, Haldorsen T. Incidence of breast cancer in Norwegian female radio and telegraph operators.  Cancer Causes Control. 1996;  7 197-204
• 35 Hansen J. Increased breast cancer risk among women who work predominantly at night.  Epidemiology. 2001;  12 74-77
• 36 Davis S, Mirick D K, Stevens R G. Night-shift work, light-at-night, and the risk of breast cancer.  J Natl Cancer Inst. 2001;  93 1557-1562
• 37 Schernhammer E S, Laden F, Speizer F E, Willett W C, Hunter D J, Kawachi I, Colditz G A. Rotating night shifts and risk of breast cancer in the Nurses’ Health Study.  J Natl Cancer Inst. 2001;  93 1563-1568
• 38 Hansen J. Light at night, shiftwork, and breast cancer risk.  J Natl Cancer Inst. 2001;  93 1513-1515
• 39 Feychting M, Osterlund B, Ahlbom A. Reduced cancer incidence among the blind.  Epidemiology. 1998;  9 490-494
• 40 Verkasalo P K, Pukkala E, Stevens R G, Ojamo M, Rudanko S L. Inverse association between breast cancer incidence and degree of visual impairment in Finland.  Br J Cancer. 1999;  80 1459-1460
• 41 Pukkala E, Verkasalo P K, Ojarno M, Rudanko S L. Visual impairment and cancer: a population-based cohort study in Finland.  Cancer Causes Control. 1999;  10 13-20
• 42 Czeisler C A, Shanahan T L, Klerman E B, Martens H, Brotman D J, Emens J S, Klein T, Rizzo J F 3rd. Suppression of melatonin secretion in some blind patients by exposure to bright light.  N Engl J Med. 1995;  332 6-11
• 43 Hatonen T, Alila-Johansson A, Mustanoja S, Laakso M L. Suppression of melatonin by 2000-lux light in humans with closed eyelids.  Biol Psychiatry. 1999;  46 827-831
• 44 Jean-Louis G, Kripke D F, Cole R J, Elliot J A. No melatonin suppression by illumination of popliteal fossae or eyelids.  J Biol Rhythms. 2000;  15 265-269
• 45 Erren T C, Piekarski C. New options to test the melatonin hypothesis.  Epidemiology. 1999;  10 785
• 46 Rose G. Sick individuals and sick populations.  Int J Epidemiol. 1985;  14 32-38
• 47 Wynder E L, Stellman S D. The „over-exposed” control group.  Am J Epidemiol. 1992;  135 459-461 (5)
• 48 Brzezinski A. Melatonin in humans.  N Engl J Med. 1997;  336 186-195