Does Light Have a Dark Side?
Nighttime illumination might elevate cancer risk
By J. Raloff
Since life began, one pattern has
dominated Earth’s natural environment—a daily rhythm of intense sunlight
alternating with nights of near-total darkness. As a source of heat and energy, sunlight
powers a majority of the planet’s biological activities. When that light disappears,
much of the world rests.
Humans, the grand manipulators, have
not been content to cede control of their activity cycle to the heavens, however. People
have spent eons developing ever better means to artificially extend the day. Thanks to
widespread electrification and color-corrected, high-watt lightbulbs, synthetic sunlight
can now bombard city dwellers around-the-clock.
This attempt to erase the
night—or at least to confine it to small, artificially defined windows—may come
with a price. At a minimum, it can lead to a chronic lack of sleep, diminishing the
effectiveness of the body’s immune system. Some new studies, however, suggest the
possibility of an even more worrisome threat.
Exposure to light at night can
disrupt the body’s production of melatonin, a brain hormone best known for its daily
role in resetting the body’s biological clock (SN: 5/13/95, p. 300). Secreted
primarily in the brain, and at night, melatonin triggers a host of biochemical activities,
including a nocturnal reduction in the body’s production of estrogen. Some
researchers have speculated that chronically decreasing nocturnal melatonin
production—as with light—might increase an individual’s risk of developing
estrogen-related malignancies, such as breast cancer.
Two studies in Nordic populations
now offer tentative support for this idea.
According to neuroendocrinologist
Russel J. Reiter of the University of Texas Health Science Center at San Antonio, the
emerging science indicates that, functionally, "light is a drug"—and that
"by abusing it, we risk imperiling our health."
Light entering the eye allows our
brains to sense the shape, size, color, and motion of objects around us. It also summons,
albeit imperceptibly, a cadre of other biological sentinels. These go on to trumpet
light’s presence to distant tissues—organs and cells lacking the means to detect
illumination directly.
When these biochemical fanfares
occur late at night, they can alter the timing of melatonin’s peak output, as a
landmark study in 1980 showed. Alfred J. Lewy and his colleagues at the National Institute
of Mental Health in Bethesda, Md., shut down melatonin production in men by waking and
exposing them to 2,500 lux of white light at 2 a.m., when synthesis of the hormone was at
its peak. (For perspective, 100 lux may be found in a comfortably dim living room, whereas
sunlight at high noon on a cloudless day can blast the eyes with 100,000 lux.) At the
Oregon Health Sciences University in Portland, 8 years later, Lewy and George C. Brainard,
now at Thomas Jefferson University in Philadelphia, found that just 50 lux could do the
same trick—if it is green light.
At about the time this work was
going on, Richard G. Stevens of the Energy Department’s Pacific Northwest National
Laboratory in Richland, Wash., was developing a controversial theory now known as the
melatonin hypothesis. It holds that long-term environmental perturbations in natural
rhythms of melatonin secretion—by exposure to electromagnetic fields (SN: 1/10/98, p.
29) or to light at night—might increase cancer risk, especially in the breast, by
increasing estrogen exposure.
Since the theory’s debut,
researchers have shown in animals that melatonin also functions as an antioxidant (SN:
8/14/93, p. 109) and an anticarcinogen. Some rodent studies have also demonstrated that
certain nascent cancers grow more rapidly when the animals encounter even low levels of
light at night (see sidebar).
The first preliminary evidence
linking light to cancer in people emerged 8 years ago in a report by Robert A. Hahn of the
Centers for Disease Control and Prevention in Atlanta. After combing statistics from a
national survey on women who had been hospitalized between 1979 and 1987—including
some 11,700 with breast cancer—he computed the incidence of this malignancy in blind
and sighted women. If light alters cancer risk through some disruptive effect on
melatonin, the epidemiologist reasoned, people whose eyes can’t detect light should
prove resistant. As a further test, he looked at heart-disease incidence, where melatonin
should play no role.
In the May 1991 EPIDEMIOLOGY,
Hahn reported that although the profoundly blind women proved as likely as the sighted
women to get heart disease, they appeared only half as prone to develop breast cancer.
Probing this idea in more detail,
Maria Feychting and her colleagues at the Karolinska Institute in Stockholm have just
compared cancer incidence in 1,600 profoundly blind men and women with that in 13,000
people having severe visual impairment. Because members of the second group could still
perceive light, Feychting explains, they should resemble sighted people in terms of any
light effects on melatonin.
In the September EPIDEMIOLOGY,
her team now reports finding that, as predicted, cancer incidence among the visually
impaired individuals was virtually identical to that in Sweden’s general population.
People who were unable to detect light faced only 70 percent of that cancer risk.
Among profoundly blind men, the
lower incidence showed up largely in cancers of the prostate, stomach, colon, rectum,
skin, and lung. Among profoundly blind women, less cancer occurred in the breast, ovaries,
and stomach.
The variety of cancers affected was
unexpected. Feychting had anticipated that any change in cancer rates would trace to
melatonin’s influence on the body’s production of estrogen (SN: 7/3/93, p. 10).
High lifetime exposure to estrogen can spur the development of certain cancers, notably
breast cancer. Instead, she now observes, melatonin may have a more general
cancer-suppressing role.
A new Finnish study also compares
cancer incidence among profoundly blind people with rates in visually impaired men and
women. Slated for publication in the November CANCER CAUSES AND CONTROL, the study
found an even more sharply reduced incidence of breast cancer among people unable to
perceive light than was seen in the Swedish study. It also found that cancer incidence
rates in people with minor visual impairment "were rather close to those in the
general population," notes Eero Pukkala, an epidemiologist with the Finnish Cancer
Registry in Helsinki and one of the report’s authors.
"Throughout the visual
categories, we also see a nice trend of decreasing breast cancer risk with decreasing
vision," he says. Indeed, this would make sense, argues Stevens, if the eyes of the
more visually impaired individuals actually take in or sense less light—as occurs in
many eye diseases.
However, in sharp contrast to the
Swedish analysis, Pukkala notes, profoundly blind individuals in his study showed no
reduction in cancer risk for sites other than the breast. Because the Finnish study
analyzed the same types of data as the Swedish study, and in a group of comparable size,
he is perplexed by the dissimilarity in their findings for sites other than the breast.
Although the findings of both
studies are consistent with the premise that melatonin disruption by light promotes at
least breast cancer in humans, Feychting and Pukkala acknowledge that both analyses fall
far short of proving it. Their new studies are merely an initial probe of the potential
link. Pukkala now plans a larger analysis, pooling data on blind and visually impaired
individuals throughout the Nordic countries. He’s hoping it will at least home in on
the reasons for the discrepancies between the current studies—which he suspects trace
to "differences in life habits" between Swedes and Finns such as nutrition,
medical care, or social factors.
Such discrepancies also might arise
because some blind people may respond to light—even though they did not perceive
it—by altering their melatonin-production cycles. Similarly, some sighted people may
have abnormal rhythms. Neither Nordic study had the resources to measure each
participant’s daily cycle of melatonin production—a lengthy and cumbersome
procedure that requires frequent, round-the-clock sampling of blood or urine.
Steven W. Lockley, a chronobiologist
at the University of Surrey in England, and his colleagues have made such measurements.
And in the November 1997 Journal of CLINICAL ENDOCRINOLOGY AND METABOLISM, they
noted that melatonin cycles in the blind are anything but predictable.
His group recruited 49 legally blind
individuals to participate in a roughly month-long trial. Each collected his or her urine
over a 48-hour span each week. The scientists then measured a melatonin byproduct in the
urine.
Among the 30 people unable to
perceive light, 57 percent had a free-running rhythm—a cycle longer or shorter than
24 hours. "This included every single subject that we’ve studied who has had
their eyes removed," he notes. Another 23 percent had a normally cycling clock, with
melatonin reliably peaking at night. The remainder had abnormal or unclassifiable cycles.
Even among the 19 people in the
study who could perceive light, 26 percent exhibited abnormal rhythms, with melatonin
production peaking at times other than the middle of the night.
"So one can’t assume that
the melatonin rhythm in all blind people . . . is free-running—or that its peaks in
light-sensitive individuals will be normal," observes neuroendocrinologist David E.
Blask of the Mary Imogene Bassett Research Institute in Cooperstown, N.Y.
Blask’s studies of rats suggest
that an abnormal timing of melatonin peaks can have a powerful effect on cancer.
He administered cancer-causing
chemicals to rats and then over subsequent weeks injected the animals daily with
melatonin. The injections were timed to produce peaks during daylight hours, when
melatonin concentrations should have been negligible.
When those injections occurred
mid-morning, tumors grew at the same rates seen in animals not receiving injections.
However, in animals that received the hormone during the afternoon, "we see an
inhibitory effect of the hormone on tumor growth, not only in liver cancers, but also in
breast cancers."
The findings suggest "that
there is a rhythm of sensitivity within tumor tissues or in cells susceptible to becoming
tumors," he told Science News. "And maybe in people who can’t
perceive light, the oscillating cycle of their biological clock causes their melatonin
peaks to coincide with the inhibitory period of tumor cells more often than they do in
light-sensitive people."
The growing body of data on
melatonin, light, and cancer suggests that certain populations, such as shift workers or
others who regularly work in bright light at night, could face unusual risks, Blask
argues. Certainly, he says, "the data are suggestive enough to raise eyebrows and
prompt further serious study."
William S. Baldwin and J. Carl
Barrett of the National Institute of Environmental Health Sciences in Research Triangle
Park, N.C., agree that such theories should be tested—by probing the most likely
mechanisms of light’s effects. "When the melatonin hypothesis was first
presented," the pair notes, "no putative melatonin receptors [on cells] were
known." Since then, three types have been identified.
In the March MOLECULAR
CARCINOGENESIS, they lay out the molecular basis for concerns that light at night
might prove an endocrine disrupter with the potential to increase cancer risk. They note
that recent findings in several laboratories working with cells and with tissues removed
from animals indicate that a reduction of melatonin can alter the production of other
hormones, may suppress the immune system’s ability to recognize and respond to newly
emerging cancers, and appears to spur the growth of at least some tumor tissues.
By studying which cells possess
melatonin receptors and how cells use them to respond to the hormone—as
Barrett’s team and others are now doing—science may resolve whether night-time
illumination truly threatens health, and if so, how much and in whom.
Studies now under way are also
testing which wavelengths—or colors—are most biologically active. For instance,
blue and green light appear especially effective at inhibiting melatonin synthesis in
healthy young men, according to studies by Brainard. Indeed, he notes that for some
colors, "17 lux was sufficient to produce strong melatonin suppression in these
men—and some had full suppression with exposure to as little as 5 lux." The
latter "is a little more illumination than what you’d have with full
moonlight."
Brainard notes that the payoff for
finding out what wavelengths are most hormonally disruptive could be insights on how
"to tailor nighttime lighting to provide good vision without interfering with the
melatonin rhythm." He says that "it may also help us develop more effective
lights for use in treating winter depression and sleep disorders."
Does Light Have a Dark Side?
At least in rats, a little light
throughout the night can have a dramatic impact on cancer, observes David E. Blask of the
Mary Imogene Bassett Research Institute in Cooperstown, N.Y.
Tumors can grow especially rapidly
in rodents exposed to constant light, he notes—presumably because of a near-total
suppression of their melatonin. To test just how much light was necessary to enhance tumor
growth, he implanted liver-cancer cells into rats.
His team housed one group of caged
animals in a room illuminated around-the-clock with about 850 lux of white light, which is
roughly equivalent to an office with medium lighting. A second group of animals spent
their days in 850 lux but their nights in total darkness. A third group encountered almost
the same light-dark cycle. The only difference: 0.2 lux leaked in at the bottom of the
door to their room from a hallway outside—illumination well below that typical of a
moonless night, he says.
In the October 1997 LABORATORY
ANIMAL SCIENCE, Blask’s team reported that tumors in animals exposed to the crack
of light coming under the room’s door grew almost twice as fast as those in animals
getting a night of total darkness. Indeed, he says, "animals exposed to the low-level
light contamination had a tumor-growth rate virtually identical to that in the animals
exposed to bright, constant light." He has just replicated the findings in an
experiment in which the lighting was more rigorously controlled.
References:
Baldwin, W.S., and C. Barrett. 1998.
Melatonin: Receptor-mediated events that may affect breast and other steroid
hormone-dependent cancers. Molecular Carcinogenesis 21(March):149.
Dauchy, R.T. . . . D.E. Blask, et al.
1997. Light contamination during the dark phase in "photoperiodically
controlled" animal rooms: Effect on tumor growth and metabolism in rats. Laboratory
Animal Science 47(October):511.
Feychting, M., B. Österlund, and A. Ahlbom.
1998. Reduced cancer incidence among the blind. Epidemiology(September):490.
Hahn, R.A. 1998. Does blindness protect
against cancers? Epidemiology 9(September).
______. 1991. Profound bilateral blindness
and the incidence of breast cancer. Epidemiology 2(May):208.
Lockley, S.W., et al. 1997.
Relationship between melatonin rhythms and visual loss in the blind. Journal of
Clinical Endocrinology and Metabolism 82(November):3763.
Further Readings:
1995. Hormones help elderly sleep. Science
News 148(Sept. 9):175.
Brainard, G.C., et al. 1988.
Dose-response relationship between light irradiance and the suppression of plasma
melatonin in human volunteers. Brain Research 454:212.
Coleman, M.P., and R.J. Reiter. 1992. Breast
cancer, blindness and melatonin. European Journal of Cancer 28:501.
Lewy, A.J., et al. 1980. Light
suppresses melatonin secretion in humans. Science 210(Dec. 12):1267.
Raloff, J. 1998. EMF's biological influences. Science News
153(Jan. 10):29.
______. 1996. Eyes possess their own
biological clock. Science News 149(April 20):245.
______. 1995. Drug of darkness. Science
News 147(May 13):300.
______. 1993. EcoCancers. Science News
144(July 3):10.
Ruberg, F.L. . . . G.C. Brainard. 1996.
Melatonin regulation in humans with color vision deficiencies. Journal of Clinical
Endocrinology and Metabolism 81(August):2980.
Weiss, R. 1989. Recent awakenings in
melatonin research. Science News 136(Nov. 11):317.
The National Science Foundation Center for
Biological Timing Home Page is available at http://www.cbt.virginia.edu/index.html.
Sources:
J. Carl Barrett
National Institute of Environmental Health Sciences
Laboratory of Molecular Carcinogenesis
P.O. Box 12233
Research Triangle Park, NC 27709
George C. Brainard
Thomas Jefferson University
Neurology Department
Jefferson Medical College
Philadelphia, PA 19107
Maria Feychting
Institute of Environmental Medicine
Box 210
S-171 77 Stockholm
Sweden
Eero Pukkala
Institute for Statistical and Epidemiological Cancer Research
Finnish Cancer Registry
Liisankatu 21 B
FIN-00170 Helsinki
Finland
Russel J. Reiter
University of Texas Health Science Center, San Antonio
Department of Cellular and Structural Biology
7703 Floyd Curl Drive
San Antonio, TX 78284-7762
Richard Stevens
Pacific Northwest National Laboratory
Richland, WA 99352
From Science News, Vol. 154, No. 16, October 17, 1998, p. 252.