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Editorial 2002; 23(Suppl 2): 71-78 PubMed PMID: 12163852 Citation  Keywords:  Darkness, Decision Making, Humans, Light:adverse effects, Neoplasms:epidemiology, Neurosecretory Systems:physiology, Risk Factors,.   

: Research on light at night and cancer is evolving at an accelerating pace, fueled largely by exciting results in rodent toxicology and basic human biology. Epidemiologic research is at a relatively early stage of development in which the exposure surrogates such as shift work and blindness predominate. Causal graphs for shift work, light at night and breast cancer illustrate some of the subtleties that can arise in the use of exposure surrogates of different kinds. Baseline data on circadian rhythms and melatonin cycles among human populations living at different latitudes are needed. Epidemiologic study of this topic is expected to mature soon as studies begin to incorporate quantitative and semiquantitative measurements and personal histories of exposure to light at night. The current emphasis on breast cancer should widen to include other cancers and intermediate outcomes. An advance in epidemiologic studies of blind persons would be to compare cancer rates between the "cortically blind" and the "retinally blind" within levels of visual impairment. Without a proposed intervention to reduce exposure to light at night, attributable fraction and attributable caseload estimates are meaningless. In the near future, both epidemiologic and laboratory research in this area are expected to grow appreciably in scope and scale....

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Journal Article 2002; 23(Suppl 2): 57-60 PubMed PMID: 12163850 Citation  Keywords:  Breast Neoplasms:epidemiology, Circadian Rhythm, Female, Humans, Light:adverse effects, Lighting, Risk Factors,.   

: Risk of breast cancer varies by about 5-fold among societies, and incidence and mortality have been increasing worldwide for many decades. Migrants from low-risk Asian societies to the U.S. suffer elevated risk of breast cancer in their own lifetimes, and the second or third generation Asian-Americans attain the high risk of the multi-generational European immigrants [1,2]. Something about a modern Western lifestyle apparently increases risk dramatically. Madigan et al. [3] estimate that 41% of the new U.S. cases of breast cancer are explained by "known risk factors"; these include the reproductive factors of age at first birth, menarche, menopause. They ascribe about 30% to reproductive factors when they are analyzed alone. "High income" is estimated to account for about 19% when analyzed by itself. The 41% is an analysis taking all the factors together, and since they are related, the total is less than the sum of estimates for the individual items. By itself, "High income" has no biological interpretation and must reflect attributes of lifestyle and/or environment that increase risk. So, the proportion of breast cancer cases in the U.S. that can be accounted for by known biological risk factors is about one third. Therefore, at least half of breast cancer risk in the U.S., and other Westernized/industrialized societies, is in excess of that found in non-industrialized societies and is without any agreed-upon explanation. Many candidate factors exist, each with a cadre of proponents. The sum of these may turn out to explain the bulk of the excess risk in modern societies. On the other hand, they may not, and worse, may fall woefully short....

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Journal Article 2002; 23(Suppl 2): 52-56 PubMed PMID: 12163849 Citation  Keywords:  Animals, Darkness, Humans, Light:adverse effects, Melatonin:physiology, Neoplasms:physiopathology, Photoperiod, Pineal Gland:physiology,.   

: Over the past few years, we have shown that the surge of melatonin in the circulation during darkness represents a potent oncostatic signal to tissue-isolated rat hepatoma 7288CTC, which is an ER+ adenocarcinoma of the liver. This oncostatic effect occurs via a melatonin receptor-mediated suppression of tumor cAMP production that leads to a suppression of the tumor uptake of linoleic acid (LA), an essential fatty acid with substantial oncogenic properties. The ability of LA to promote cancer progression is accomplished by its intracellular metabolism to 13-hydroxyoctadecadienoic acid (13-HODE) which amplifies the activity of the epidermal growth factor receptor/mitogen-activated protein kinase pathway leading to cell proliferation. By blocking tumor LA uptake, melatonin effectively blocks the production of 13-HODE and thus, markedly attenuates tumor growth. A similar effect of melatonin is observed in tissue-isolated, ER+ MCF-7 human breast cancer xenografts and nitrosomethylurea (NMU)-induced rat mammary cancers. When male rats bearing tissue-isolated hepatomas are exposed either to constant bright light (300 lux) or dim light (0.25 lux) during the dark phase of a 12L:12D photoperiod, the latency to onset was significantly reduced while the growth of tumors was markedly increased over a 4 wk period as compared with control tumors in 12L:12D-exposed rats. In constant light- and dim light during darkness-exposed rats, melatonin levels were completely suppressed while tumor growth, LA uptake and 13-HODE production were markedly increased. Similar results were obtained in constant bright light-exposed female rats bearing tissue-isolated NMU-induced mammary cancers or MCF-7 human breast cancer xenografts. To date, these studies provide the most definitive experimental evidence that light exposure during darkness increases the risk of cancer progression via elimination of the nocturnal melatonin signal and its suppression of tumor LA uptake and metabolism to 13-HODE....

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Journal Article 2002; 23(Suppl 2): 28-36 PubMed PMID: 12163845 Citation  Keywords:  Animals, Humans, Light:adverse effects, Melatonin:physiology, Neoplasms:etiology, Photoperiod, Pineal Gland:physiology,.   

: The role of the modulation of the pineal gland function in development of cancer is discussed in the review. An inhibition of the pineal function with pinealectomy or with the exposure to the constant light regimen stimulates mammary carcinogenesis, whereas the light deprivation inhibits the carcinogenesis. Epidemiological observations on increased risk of breast cancer in night shift workers, flight attendants, radio and telegraph operators and on decreased risk in blind women are in accordance with the results of experiments in rodents. Treatment with pineal indole hormone melatonin inhibits carcinogenesis in pinealectomized rats or animals kept at the standard light/dark regimen (LD) or at the constant illumination (LL) regimen....

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Journal Article 2002; 23(Suppl 2): 17-22 PubMed PMID: 12163843 Citation  Keywords:  Breast Neoplasms:epidemiology, Circadian Rhythm:physiology, Female, Humans, Light, Melatonin:physiology, Photoreceptor Cells, Vertebrate:physiology, Risk Factors,.   

: The impact of breast cancer on women across the world has been extensive and severe. As prevalence of breast cancer is greatest in industrialized regions, exposure to light at night has been proposed as a potential risk factor. This theory is supported by the epidemiological observations of decreased breast cancer in blind women and increased breast cancer in women who do shift-work. In addition, human, animal and in vitro studies which have investigated the melatonin-cancer dynamic indicate an apparent relationship between light, melatonin and cancer, albeit complex. Recent developments in understanding melatonin regulation by light in humans are examined, with particular attention to factors that contribute to the sensitivity of the light-induced melatonin suppression response. Specifically, the role of spectral characteristics of light is addressed, and recent relevant action spectrum studies in humans and other mammalian species are discussed. Across five action spectra for circadian and other non-visual responses, a peak sensitivity between 446-484 nm was identified. Under highly controlled exposure circumstances, less than 1 lux of monochromatic light elicited a significant suppression of nocturnal melatonin. In view of the possible link between light exposure, melatonin suppression and cancer risk, it is important to continue to identify the basic related ocular physiology. Visual performance, rather than circadian function, has been the primary focus of architectural lighting systems. It is now necessary to reevaluate lighting strategies, with consideration of circadian influences, in an effort to maximize physiological homeostasis and health....

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Editorial 2002; 23(Suppl 2): 4-6 PubMed PMID: 12163840 Citation  Keywords:  Congresses as Topic, Humans, Neuroendocrinology:organization & administration, Societies, Medical,.   

: The international meeting Light, Endocrine Systems and Cancer--Facts and Research Perspectives was convened because recent research suggests that ubiquitous light may have more serious cancer consequences than expected. Beyond the established causal link between (over) exposure to sunlight and skin cancer, many scientists consider a causal relationship between light, endocrine systems and internal cancers as biologically plausible. To identify options to turn biological plausibility of mechanisms into true understanding and to assess the possible public health relevance we chose to bring together leading specialists from clinical, experimental laboratory and epidemiological studies of these issues to stimulate a critical, multi-disciplinary discussion of published and new results. Presentations at the symposium covered the physics of light and evolutionary aspects and provided intriguing information about chronobiology, physiology and patho-physiology of endocrine systems and carcinogenesis. Experimental and epidemiological findings on light and skin cancer, and of very recent investigations of relationships between light and internal cancers such as breast cancer were presented. The meeting concluded with a lively discussion of future research options. The symposium's essence and constructive atmosphere are captured in these proceedings [Neuroendocrinol Lett 2002 Jul;23 Suppl 2:1-104] which contain: (i) original presentation papers [Vladimir Anisimov, David Blask, Roland Böni, George Brainard, Thomas Erren, Alexander Lerchl, Sidney Perkowitz, Chris Portier, Russel Reiter, Richard Stevens, Günter Vollmer]; (ii) abstracts of oral and poster presentations; (iii) four commentaries [Charles Poole, Chris Portier, Till Roenneberg and Rob Lucas, Vladimir Anisimov and Johnni Hansen] on the presentations at the meeting and possible implications for research and public health. In our view, the biological plausibility of mechanistic links between light and hormones and cancer can serve as a unique basis for syn-disciplinary research and we expect that investigations in this area will become a higher priority research focus....

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Journal Article 2002; 23(3): 259-261 PubMed PMID: 12080289 Citation  Keywords:  Biogenic Monoamines:blood, Dopamine:blood, Epinephrine:blood, Hallucinogens:adverse effects, Humans, Hydroxyindoleacetic Acid:blood, N-Methyl-3,4-methylenedioxyamphetamine:adverse effects, Norepinephrine:blood, Psychoses, Substance-Induced, Serotonin:bloo.   

: Recreational use of the synthetic methamphetamine derivative MDMA (3,4-methylenedioxymethamphetamine), the main constituent of the illegal drug "ecstasy", has increased dramatically in recent years. The reasons for ecstasy-associated cardiovascular complications like tachycardia, arrhythmias and hypertensive crises and psychiatric symptoms like psychotic episodes are not well understood. We have measured the plasma concentrations of 5-HIAA, 5-HT, norepinephrine, epinephrine and dopamine in 159 ecstasy users and controls. Ecstasy users showed elevated resting sympathetic activity, reflected in increased norepinephrine, epinephrine and dopamine levels. The levels of these catecholamines correlated positively with the cumulative dose and also with consumption during the last 30 days and 12 months. Although it is known that significant changes in 5-HT and 5-HIAA appear in the cerebrospinal fluid in ecstasy users, we could not detect alterations in serotonergic neurotransmitters in plasma in this large sample of subjects. Thus, in the drug-free interval, ecstasy users show lowered central serotonergic activity (lowered 5-HT and 5-HIAA concentrations in CSF) along with unchanged central noradrenergic and dopaminergic activity (HVA and MHPG unchanged in CSF) and elevated peripheral noradrenergic, dopaminergic and adrenergic activity along with unchanged peripheral serotonergic activity (plasma levels). We conclude, that the data presented here could argue for a noradrenergic hyperreactivity in the drug-free interval in ecstasy users resulting from previous ecstasy consumption. Also for an association with psychotic episodes and cardiovascular complications like tachycardia, arrhythmias....

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Journal Article 2002; 23(3): 231-237 PubMed PMID: 12080284 Citation  Keywords:  Altitude, Animals, Animals, Newborn, Hypoxia:pathology, Male, Mitochondria:physiology, Organ Size, Rats, Rats, Wistar, Testis:chemistry, Testosterone:analysis,.   

OBJECTIVE: To investigate the effects of continued hypoxia on postnatal development of the rat testis.

DESIGN: Wistar rats were exposed to simulated hypoxia from birth to postnatal day (PND) 45. Testosterone (T) in the plasma and the testis was measured in rats at PND 3, 7, 14, 21, 28, 35 and 45 respectively. Testis histology and cellular ultrastructure were studied.

RESULTS: a) Hypoxia induced a significant arrest of testes weight gain after PND 28; b) T release was significantly attenuated after PND 21; c) Alterations in histology and cellular ultrastructure were found in the testis, showing the swelling of testis interstitium and the enlargement of mitochondria in Leydig cells.

CONCLUSION: Postnatal hypoxia stress alters testis development both in terms of function and structure, especially at the critical age of gonadal development....

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