The Biology of . . . Sunscreen
Nature teaches biologists how to beat back the sun and repair what it damages
By Ingfei Chen|Sunday, June 01, 2003
RELATED TAGS: GENETICS
In the United States, ultraviolet rays cause most of the 1.3 million cases of skin cancer diagnosed every year. Melanomas, the deadliest of these cancers, are on the rise.
Photograph by Martin Parr/Magnum Photos.
Daniel Yarosh likes to describe himself as "tanning challenged." Pale and lightly freckled, with blue eyes and brown hair, he is religious about wearing sunscreen lotion and encourages the same behavior in his children. His goal, he tells them, is to be "the whitest man on the planet."
Yarosh's caution stems in large part from his profession. He is a photobiologist, expert in the precise ways in which solar radiation ravages human skin. As founder of AGI Dermatics, a small biotech firm in Freeport, New York, Yarosh has been working for 25 years on a bold new treatment for sun damage: an after-sun lotion that can reverse the molecular havoc ultraviolet rays wreak within skin cells.
One in five Americans now develops skin cancer at some point in his or her life, and the sun is usually to blame. In the summer, in areas like Los Angeles and San Diego, a quadrillion photons of ultraviolet-B radiation bombard every square centimeter of exposed skin every second. Each photon has the potential to cause trouble: UV-B rays can injure DNA and dampen the immune system, allowing cells to morph into tumors.
Dermatologists say that sunscreens are among our best weapons against such cancers. In sun-scorched Australia, where deaths from melanoma rose steadily after the 1930s, the epidemic seems to be abating, thanks in part to a nationwide push for sunscreen use. Among people under the age of 60, the incidence of the disease began to level off or fall in the 1990s. Still, sunscreens aren't enough to block out the sun completely, and most people aren't willing to wear hats and long-sleeved shirts in summer. The solution, scientists like Yarosh believe, lies in the natural sun-defense strategies that microbes, plants, and other organisms have evolved.
Compounds that absorb and neutralize ultraviolet beams are ubiquitous in nature, from flavonoids in plants to the melanin that colors human skin. Some of the first sunscreen ointments, developed in the early 1900s, contained UV absorbers such as quinine from the bark of South American cinchona trees and cinnamates from cinnamon trees. More recently, researchers have studied compounds from creatures that bask continually in the tropical sun: coral reefs. In the mid-1980s, environmental biochemist Walter Dunlap and a colleague at the Australian Institute of Marine Sciences in Townsville, Queensland, reported that corals rely on powerful UV-B absorbers, known as mycosporinelike amino acids, or MAAs.
"Corals that grow on the surface of the ocean have very, very high concentrations of these compounds," Dunlap says. "But as you go deeper, the concentrations diminish." MAAs, it turns out, are found in just about every marine organism. Fish even have them in the lenses of their eyes.
Based on Dunlap's work, a company in New South Wales called Sunscreen Technologies has developed a lotion called Corasol that will make its debut overseas next year. Corasol's key ingredient—a synthetic cousin of MAAs—is highly efficient at capturing sunlight, absorbing it, and dissipating the energy. Other UV absorbers tend to trigger rashes and allergies when used in high doses, so commercial sunscreens have limited potency. Corasol, by contrast, is easily tolerated, and its formula is exceptionally stable.
Even the most powerful sunscreen can't always afford enough protection: If people put on too little of it—and most do—the sun will get through. That creates a need for Yarosh's after-sun lotion. It takes advantage of a line of defense found in almost all living organisms: enzymes that fix DNA damage.
Solar radiation warps the chains of nucleotide bases, known as purines and pyrimidines, that form DNA. When two neighboring pyrimidines absorb UV-B energy, they often fuse into lesions known as dimers. Dimers spur the release of cytokines—proteins that rouse inflammation yet suppress the immune system. If too much DNA damage accrues, the cells begin to self-destruct. That's what the peeling skin of a bad sunburn seems to be—a mass suicide of cells. In the cells that survive, dimers can give rise to DNA mutations that cause cancer.
Sea urchins acquire natural sunscreens called MAAs by gobbling algae that contain them. Can people do the same? Marine physiologist J. Malcolm Shick of the University of Maine tried eating like an urchin: "I was munching dried red algae all the time." But skin biopsies revealed no MAAs.
Fortunately, our cells have sophisticated machinery for fixing most dimers. When lesions occur, more than 20 kinds of enzymes rush in to cut them out and replace them with fresh nucleotides. "It's a very powerful system," Yarosh says. "The rule of thumb is that when a person gets a typical sunburn, it takes 24 hours to remove half the damage."
DNA repair isn't a flawless system, even in healthy skin. Some studies have suggested that fair-skinned people are more prone to skin cancer because their skin is less adept at DNA repair. Yarosh's lotion, called Dimericine, bolsters the process with the enzyme T4 endonuclease V. It is found in bacteriophages, viruses that infect Escherichia coli bacteria. The enzyme homes in on only UV-induced dimers, snipping lesions at one end and detaching them from the DNA's backbone. The cell's normal repair apparatus then finishes the job.
To get T4 endonuclease V into the skin—no easy feat—Yarosh's team at AGI Dermatics packaged it inside liposomes, microscopic beads of fat that squeeze down into the epidermis and keratinocyte cells. (The beads don't penetrate deeply enough to reach the blood vessels.) The cells break down the enzyme quickly after it has done its work. "In a day, the enzyme's gone," Yarosh says.
Dimericine appears to increase dimer repair and help prevent immunosuppression and the release of cytokines. In a clinical trial three years ago, 20 patients suffering from xeroderma pigmentosum, a disease that raises the risk of skin cancer by 1,000 times, applied the lotion daily and nine did not. After one year, the group that used the lotion had 68 percent fewer precancerous skin lesions and 30 percent fewer basal cell carcinomas—the most common skin tumors. No adverse effects were observed.
Dimericine is like a "morning-after pill," says immunologist Stephen Ullrich of the M.D. Anderson Cancer Center in Houston. "Let's face it, we've all done this: You go out and you don't put on enough sunscreen, or you don't reapply it, and you get burned. So how do you prevent the damage? Well, one approach is Dan's liposomes."
The Food and Drug Administration is reviewing Dimericine as a treatment for xeroderma pigmentosum and has requested more data on its effectiveness and manufacturing. Meanwhile at Novogen, an Australian pharmaceutical company near Sydney, a different post-sun remedy is in the works. Known as equol, the compound is a metabolite of a flavonoid found in soybeans and red clover. In studies of hairless mice conducted at the University of Sydney, applications of equol after UV exposure reduced sunburn and inflammation, immunosuppression, and the development of skin tumors.
Equol is now being tested on a dozen or so human volunteers. Preliminary results look promising, although it's still unclear exactly how the extract works. According to cancer epidemiologist David Whiteman of the Queensland Institute of Medical Research in Herston, skin biopsies suggest that equol boosts the production of metallothioneins, which cells normally crank out in response to UV light. Metallothioneins are antioxidants that "mop up the reactive oxygen molecules" that are generated by UV photons and damage DNA, Whiteman says. Equol also appears to enhance DNA repair.
"It's still in its early days," Whiteman says. But if natural sunscreens and after-sun lotions prove effective, they might turn sunbathing into less of an extreme sport. They may even give Dan Yarosh some competition for the title of whitest man on Earth.
The slick Applied Genetics site has information on Dimericine, Daniel Yarosh's skin-care product: www.agiderm.com/derm.html.
Sunscreen Technologies' Web site traces the origins of Corasol and suggests some potential nondermatological uses for the product—for example, as a protective coating on building materials, fabrics, and other substances that are affected by the sun's rays: www.sunscreentech.com.
While the Novogen site deals primarily with their existing products, it does have a little bit of background on equol: www.novogen.com/pharma/pharma0401.cfm?mainsection=04⊂section=05.
The Centers for Disease Control offers consumer-oriented information on limiting sun exposure, preventing skin cancer, and selecting sunscreens, geared to both children (www.cdc.gov/ChooseYourCover/SunDay-brochure.htm) and adults (www.cdc.gov/cancer/nscpep/index.htm).
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