The Darker Side of Sunlight
The threat of melanoma is not to be taken lightly.
By Kathleen Kocks
Photo inset: This 4-by-8 millimeter spreading melanoma displays the typical
characteristics described by the ABCDE method of recognizing melanoma.
Signs that a mole or spot may be early melanoma include Asymmetry,
Border irregularity, Color variability, a Diameter larger than a
pencil eraser, and Evolution of the spot, i.e., it changes in size,
shape, color, or other symptoms (such as itching, bleeding, tenderness,
or changes in elevation). Photo courtesy of the National Cancer Institute.
Humans are naturally drawn to the comfort of a sunny
day. But according to a new discovery by two GW research
professors, there is one more reason to avoid basking
in the sun.
In a paper published in the September 2001 edition of
Nature and in the September 2004 journal Cancer
the husband-and-wife team of Edward C. De Fabo and Frances
P. Noonan identified ultraviolet B light as the waveband
active in initiating cutaneous malignant melanoma, the
most aggressive and most lethal form of skin cancer.
Additionally, the pair determined that UVB exposure at
an early age was critical in initiating melanoma.
The paper, titled “Ultraviolet B but not Ultraviolet
A Radiation Initiates Melanoma,” also reported
that ultraviolet A light had no role in initiating melanoma,
even at relatively high doses. Furthermore, data seemed
to indicate that UVA light might even inhibit the growth
of melanoma tumors.
Scientists have long suspected that UVB, the light that
causes sunburn, had a role in causing melanoma. But until
this study, no one had assessed the individual roles
of UVB and UVA in inducing melanoma in mammalian skin.
“There is somewhat of a controversy about UVA’s
role in human melanoma. For one reason, UVA is more prevalent;
the ratio of UVA to UVB in sunlight is about 20:1,” De
Fabo says. “But because we have a unique light
system which produced defined UVA or UVB and a unique
mouse model which strongly recapitulated human disease,
we feel very confident in our conclusion that UVB is
the major waveband for the initiation of melanoma.”
For their research, De Fabo and Noonan collaborated
with Thomas Fears and Glenn Merlino, both of the National
Cancer Institute. The researchers employed sunlamps,
and a unique GW-developed light system that produces
isolated UVB or UVA wavebands or solar-simulating radiation
that includes UVB, UVA, and visible light in proportions
approximating sunlight. For their animal model, they
used the first transgenic mice that, in response to UV,
produce melanomas that resemble human melanoma.
“Our transgenic mouse was developed by our collaborator
at NIH [National Institutes of Health], Dr. Glenn Merlino,
who was studying a hepatocyte growth factor. He genetically
engineered the mice so that this growth factor was overexpressed
throughout the mouse,” Noonan says. “To his
surprise, the resulting mouse had melanocytes, pigment
cells, throughout its skin, rather than only in its hair
follicles. Thus, the mouse skin was much more like human
skin. If he kept the mice until they were very old, they
started getting melanomas, but these melanomas were not
comparable to the tumors of human melanoma.”
De Fabo and Noonan’s unique GW-developed
light system, shown here with samples of paper
for demonstration purposes, serves as a “solar
simulator,” producing UVB, UVA, and visible
light in proportions that approximate sunlight.
The unique system allows the production of many
different narrow wavelengths, or colors, of different
shades throughout the ultraviolet part of the spectrum
and allows an exact shade to be spread across a
wide exposure field. It is a process that was not
previously available with other instruments.
“We obtained some of these mice around 2001 and
started irradiating them with ultraviolet light as adults,
at about six weeks old, but they made no melanoma skin
cancer. We then looked at the literature on the epidemiology
of melanoma and found that if a person gets sun exposure
as a child, they are more likely to get melanoma. So
we began UV-irradiating the mice as babies, about three
days old and, several months later, they developed melanoma,” Noonan
says. “These melanomas closely resembled human
To determine which UV waveband played the greatest role
in melanoma initiation, De Fabo and Noonan began irradiating
the infant mice with UVB only, UVA only, or a combination
of both. Comparing the data, UVB showed a significant
positive trend for initiating melanoma, whereas UVA showed
a negative, but not significantly negative trend.
It required surprisingly little radiation to initiate
melanoma. The exposure lasted only 15 minutes and the
dose given was equivalent to being exposed to two hours,
40 minutes of sunlight on July 4, 2000, in San Diego.
The mice were also irradiated with a much lower dose
of UVB (about a third less), and even this dose was very
effective in producing melanoma; five of 10 treated mice
This study is not the first to produce significant discoveries
by De Fabo and Noonan, who perform their research at
the Laboratory of Photobiology and Photoimmunology at
the GW Medical Center. Combining De Fabo’s expertise
in photobiology and Noonan’s expertise in immunology,
the pair began their research in the 1980s as one of
the first groups to study the role of UV in human health
problems. Their first discovery revealed the mechanism
of how UV light suppresses the immune system.
“Through our work, we came across urocanic acid
on human skin. At the time, the acid was known only to
absorb UV light,” De Fabo says. This led to an
assumption that it prevented UV light from penetrating
beyond the skin surface and thus offered a level of UV
protection. Some sunscreen manufacturers even included
urocanic acid in their formulas and advertised it as
a UV blocker.
De Fabo and Noonan discovered that urocanic acid had
a far different role. When urocanic acid absorbs UV,
it is altered—it isomerizes or “bends”—and
it sends a signal to the spleen and lymph nodes that
reprograms immune system cells from being attacker cells
to being suppressor cells. Urocanic acid was removed
from sunscreens and cosmetics following De Fabo and Noonan’s
reporting of its immunosuppressive effects.
Edward De Fabo and Frances Noonan in one of their Ross Hall laboratories.
“Why would nature select a biological process
that would allow tumors to grow and be harmful to the
host? One possibility is that when the skin is exposed
to sunlight and burns, the skin cells look foreign and
the immune system normally would attack them. The urocanic
acid tells the attacking army to stop, so the skin can
heal. But while the immune system is suppressed, skin
cancers or tumors can form and grow. If all things were
working the way they should, the immune system would
destroy the skin tumor right away,” De Fabo explains.
In 1983, the researchers published a paper, “Mechanism
of immune suppression by ultraviolet irradiation in vivo.
I. Evidence for existence of a unique photoreceptor in
skin and its role in photoimmunology” in the Journal
of Experimental Medicine. This paper earned De Fabo and
Noonan international recognition.
De Fabo and Noonan’s recent paper on UVB’s
role in initiating melanoma is also gathering accolades.
The Faculty of 1000, a group of scientists that regularly
reviews medical papers, rated it as excellent, its top
What’s next for this research duo? “We are
seeking a grant to do an action spectrum that would use
different wavelengths within the UV bands, to see how
effective they are for initiating melanoma. We would
also explore how various compounds in the skin absorb
different wavelengths of UV light. If we can determine
the compound that absorbs melanoma-producing wavelengths,
we would have a very powerful tool for identifying the
currently unknown photoreceptor that initiates melanoma.
When we know what that molecule is, we can do all kinds
of things, like design better sunscreens or design a
personal dosimeter that tells you when you are approaching
melanoma-producing overexposure to UV light,” De
“It’s not your run-of-the-mill approach
to disease study, because most people don’t take
light into consideration. But we now have collaborators
in the molecular area, particularly at NIH, who are studying
with us how different wavelengths of light can activate
various molecular genetic pathways that regulate cell
Looking at other research paths, Noonan says, “Now
that we have this mouse model, we could breed mice that
have other genetic changes, so we could maybe explore
how to repair DNA damage from UVB or look at other genetic
susceptibility factors involved in the incidence of melanoma.
Everyone who is sunburned doesn’t get melanoma;
it is the combination of light and genetic susceptibilities.
We would like to know what they are.”
Meanwhile, De Fabo and Noonan feel it is imperative
to stress the need to avoid overexposure to UV light.
“We know that fair-skinned people who move to
places like Australia, where there is more UV light,
get more skin cancer,” Noonan says. “It’s
not a far stretch to say if we get more UV everywhere,
then we will get more skin cancer. We truly need to protect
our children from sunburn, particularly during the first
12 years. The parameters from our research showed us
that you might need only a couple of bad burns to initiate
melanoma later in life.”
De Fabo agrees, particularly about the probability of
more UV exposure. His sentiment is based on his UV research,
as well as his research since the 1980s as a member of
many scientific committees studying global warming and
the Earth’s compromised ozone layer. For his contributions,
De Fabo won in 1997 a United Nations Environmental Program
Ozone Award. He was also one of 300 scientists who conducted
a multiyear study of dramatic global warming and ozone
layer thinning in the Arctic; a much publicized report
on the topic was issued in November 2004.
“If ozone depletion is continuing and, make no
mistake it is, then we can expect increased exposure
to and danger from ultraviolet B radiation,” De
Fabo says. “We are seeing melanoma in younger and
younger people, and the incidence of melanoma in the
United States has doubled in the past 25 years. It is
a very aggressive disease. Don’t ask for trouble
by staying out in the sun unprotected, especially with
children or if you have predisposing conditions.
“We slather our kids with sunscreens and think
it is OK for them to be outside, but sunscreens may not
protect them 100 percent, especially from UV immuno-suppression.
Just avoid overexposure to sunlight, particularly the
two hours before and the two hours after noon. That’s
the time when your kids should be inside.”
Skin Cancer Facts
- Cancer of the skin is the most common
of all cancers.
- Melanoma accounts for about 4 percent
of skin cancer cases, but it causes about 79
percent of skin cancer deaths.
- The number of new cases of melanoma
in the United States is on the rise. The American
Cancer Society estimates that in 2005 there
will be 59,580 new cases of melanoma in this
country. About 7,770 people will die of this
Source: American Cancer
Society, 2005 Facts & Figures