omen , as opposed to sighted women , do not have the pportunity for nocturnal melatonin suppression by xposure to light during the night .
Light-at-night ’ and breast cancer
riginally , it was argued that part of the rising risk of reast cancer in industrialized societies was due to inreased use of electric lighting which could suppress melatonin [ 15 ]; a suppression of melatonin was hypothezed to increase estrogen [ 16 ], and thereby increase risk . his idea was based on experiments in rodents on the ffects of constant light exposures on mammary tumorienesis [ e . g ., 17 ], and on the epidemiology of breast cancer which risk was highest in the most industrialized , and ereby most electrified , societies . However , Shah et al . 7 ] found no effect of constant light on plasma estradiol vels in rats , although melatonin administration lowered stradiol . It is not clear whether melatonin or light-at-night ffects estrogen production in humans , the data being mited and conflicted [ 18 – 25 ]. Apart from effects on estrogen production , there are everal mechanisms by which melatonin might affect reast cancer that have emerged ( reviewed in [ 26 ]). These clude direct oncostatic effects , interference with estrogen ceptor function , effects on immune function , and effects n free radical biology . In particular , an effect of light at ght , including dim light , on melatonin production can ave profound effects on growth and progression of both ansplanted liver tumors in rats [ 27 ] and transplanted uman-derived breast tumors in rats by altering linoleic cid metabolism [ 28 ]. The first study of prediagnosis melatonin level did not nd a difference between women who later developed reast cancer and those who did not [ 29 ]; the authors note , owever , that the early studies of estrogen and breast ancer were inconsistent , and it has required a combined nalysis of many studies to show that there is in fact a rong association [ 30 ]. In addition to affects on melatonin , e potential for light to alter circadian rhythm generation the suprachiasmatic nuclei ( SCN ) leads to the potential or disruption of clock gene communication with cell cycle gulation in the mammary tissue [ 4 , 31 ]. Disruption of cell ycle regulation and / or apoptosis opens a large new area or investigation of light effects on cancer risk .
ight and exogenous melatonin
uppression of the normal nocturnal surge in melatonin y exposure to light at night may increase breast cancer sk by several different mechanisms [ 26 , 28 , 32 – 34 ].
( Stress and cortisol may also play a role in circadian f spontaneous tumors , whereas C3H HeJ mice under disruption and cancer [ 35 , 36 ]) Therefore , maintenance of onstant light showed delayed spontaneous mammary a strong melatonin rhythm seems desirable . However , mor development and a longer life span . The C3H – HeJ supplementation with melatonin could result in ‘ Circadianmouse has a degenerate retina ( rd ) and is visually blind . Disruption ’ itself due to the emerging understanding of owever , it has now been shown that nocturnal melatonin the impact of exogenous melatonin on the human circadian rhythm . In fact , the circadian phase shift induced in Among the first to investigate the effect of light on
the C3H / He rd mice can be suppressed by light [ 43 ].
humans by a pharmacological bolus of melatonin can be hemically induced mammary tumors in rats was Khaetski comparable to that induced by a bright light stimulus . 44 ; as described in 45 ] who conducted experiments in Wirz-Justice et al . [ 37 ] conducted a study in which 9 hich ‘ outbred rats ’ were exposed to constant light healthy young men were subjected to one of 4 conditions : eginning at four months of age , and given dimethylenzanthracene ( DMBA ). Compared to rats on 12:12
5 mg of melatonin at 20:40 in the evening , a 3 h period of 5000 lux light beginning at 21:00 , both , or neither ght – dark ( LD ) cycle and which also received DMBA , ( with placebo for the melatonin tablet ). All nine subjects ose on constant light had reduced mammary tumor yield . received all four exposure conditions . Melatonin onset n contrast , Khaetski reported that when constant light did was then measured the day following the treatments under ot start until 4 weeks after DMBA administration , tumor a constant-routine , dim-light regime (> 10 lux ). Under the evelopment was accelerated compared to rats which light-only exposure , there was a 41 min phase delay ; ontinued on the 12:12 LD cycle . under the melatonin-only exposure , there was a 24 min Within the context of the conflicting early experiments phase advance . The two together tended to cancel each which mammary tumors were either stimulated or other : with both exposures , dim-light melatonin onset duced in rodent models , the question becomes what are ( DLMO ) was not significantly different from exposure to e factors which influence tumor yield from constant neither . ght ? In the 1980s , Shah et al . [ 17 ] conducted an elegant
Before Lewy et al . [ 38 ], it was speculated that the human pineal was insensitive to light . Since that seminal ctomy were used to investigate whether melatonin might
eries of experiments in which constant light and pineal-
work , the intensity of light at night shown experimentally xplain the effect of light . They found that constant light to be required to lower melatonin has declined to very low eginning before birth significantly increased terminal end levels [ 39 ]. uds of the female offspring at maturity , and increased
It is also becoming clear that light level during the day usceptibility to DMBA-induced mammary tumors . In an can affect melatonin secretion at night [ 40 ], and also sensitivity to a light exposure at night on suppression of ined weanling female rats from a supplier , placed one
tempt to replicate this finding , Anderson et al . [ 46 ] ob-
melatonin [ 41 ]. Hebert et al . [ 41 ] conducted an experiment roup on constant light and the other on 8:16 light / dark in which 12 young , healthy subjects ( 6 male and 6 female ) gimen , and administered DMBA when the animals were spent 1 week in a bright-day environment ( exposed to sun ) 2 days of age . In contrast to Shah et al . [ 17 ], Anderson and 1 week in a dim-day environment ( dark goggles worn ound a significant reduction in mammary tumor burden in during the day ). At the end of each week , the subject ’ s e constant light group . They also found , unexpectedly , sensitivity to melatonin suppression by light in the middle at 29 of the 50 rats in the constant light group showed of the night was assessed . On the 6th night in dim light ( < 15 lux ), a baseline of melatonin was determined by saliva sampling every 30 min . During the next night , the subjects were exposed to 500 lux light for 3 h beginning at 1 am . Percent light suppression was significantly greater after the dim week than after the bright week . However , there was a greater amplitude of melatonin production after the bright week than after the dim week .
Light and cancer in mice and rats
Among the first experimenters to investigate the impact of constant lighting on mammary tissue susceptibility to tumorigenesis was Jöchle [ 42 ]. He reported that C3H-A mice under constant light showed accelerated development mature milk glands in the mammary glands at age 141 days espite being virgin , whereas none of the 50 rats on LD howed any such structures . The reason for the different tumor response appears to e due to differences in the age of the rat at first exposure constant light which resulted in differences in mammary ssue development . This , in turn , would alter tumor suseptibility [ 47 ]. Constant light began in utero in Shah et al . 7 ], but began at age 26 days in Anderson et al . [ 46 ]. fter a replication of these exposure conditions , Russo al . [ 48 ] conducted a detailed histological examination of e mammary tissues , and found that light beginning at 6 days of age ( LL26 ) produced a very different mammary and development than light beginning in utero ( LL0 ); mong the LL26 rats , mammary gland differentiation was ramatically accelerated compared to the LL0 rats , and thereby DMBA
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13
Appendix A : White Paper – Communities Addressing Light Pollution that Affect Nighttime Military Training