Lights, chemicals, action at new lab for phototoxicology.

In the delta of southeastern Arkansas, at the National Center for Toxicological Research in Jefferson, two large laboratory rooms are bright with sunlight-not the kind that streams in through windows, but simulated solar energy from tiny lamps using an electromagnetic radiation source that closely mimics the spectrum of sunlight. There, in the heart of the new Phototoxicology Research and Testing Laboratory, hairless mice are coated with creams similar to ones used daily by millions of people in search of a more "youth-ful" appearance. The question that scientists want to answer is whether the natural acids now found in almost every skin care cream on the market may actually promote skin cancer. Researchers are concerned that these acids, known as alpha-and beta-hydroxy acids, might peel away layers of the skin to the point where sunlight can damage DNA in cells at the skin's deepest od corneum) and epider-mal tissues. According W i U to the FDA, two consequences of using creams containing these acids are increased proliferation ___ ~ of epidermal epithelial cells and deeper penetration of electromagnetic radiation into the skin, both of which raise the possibility of an increased risk of skin can cer with continued use. Says Paul C. Howard, director of the phototoxicology laboratory, "Vanity may have a price." "It became apparent after surveying the literature and consulting with colleagues that in order to understand the carcinogenic potential of the alpha-and beta-hydroxy acids, studies would have to be designed to determine the effects of these acids on ultraviolet (UV) light-indLuced skin cancer in mice," says Howard. The FDA and the NIEHS joined together to fund a facility that would allow the simultaneous exposure of the large numbers of mice required for such studies, as wx ll as future studies on compounds that mayr affect skin cancer rates. The key features of the new facilitv are two miniature suns-six-inch xenon arc lamps that operate at 6,500 watts. The. vlisible and _m UV radiation emitted from each lamp, when filtered through glass designed to simulate the earth's atmosphere, closely mimics the spectrum of solar light. Researchers at the laboratory canl expose about 5,000 mice a day to the simulated solar light. Although, says Hoxxvard, SUI1-light can be simulated on a small scale (dozens of mice per day) with cqulipmllellt found in universits laboratories, car-cino-genicity studies can be laige and are verv difficult to do. "Thie numLibers of animllals rcquircd …

In the delta of southeastern Arkansas, at the National Center for Toxicological Research in Jefferson, two large laboratory rooms are bright with sunlight-not the kind that streams in through windows, but simulated solar energy from tiny lamps using an electromagnetic radiation source that closely mimics the spectrum of sunlight.
There, in the heart of the new Phototoxicology Research and Testing Laboratory, hairless mice are coated with creams similar to ones used daily by millions of people in search of a more "youthful" appearance. The question that scientists want to answer is whether the natural acids now found in almost every skin care cream on the market may actually promote skin cancer. Researchers are concerned that these acids, known as alphaand betahydroxy acids, might peel away layers of the skin to the point where sunlight can damage DNA in cells at the skin's deepest od corneum) and epidermal tissues. According W i U to the FDA, two consequences of using creams containing these acids are increased proliferation ___~of epidermal epithelial cells and deeper penetration of electromagnetic radiation into the skin, both of which raise the possibility of an increased risk of skin can cer with continued use. Says Paul C.
Howard, director of the phototoxicology laboratory, "Vanity may have a price." "It became apparent after surveying the literature and consulting with colleagues that in order to understand the carcinogenic potential of the alphaand betahydroxy acids, studies would have to be designed to determine the effects of these acids on ultraviolet (UV) light-indLuced skin cancer in mice," says Howard. The FDA and the NIEHS joined together to fund a facility that would allow the simultaneous exposure of the large numbers of mice required for such studies, as wx ll as future studies on compounds that mayr affect skin cancer rates.
The key features of the new facilitv are two miniature suns-six-inch xenon arc lamps that operate at 6,500 watts.
The. vlisible and _m UV radiation emitted from each lamp, when filtered through glass designed to simulate the earth's atmosphere, closely mimics the spectrum of solar light. Researchers at the laboratory canl expose about 5,000 mice a day to the simulated solar light. Although, says Hoxxvard, SUI1light can be simulated on a small scale (dozens of mice per day) with cqulipmllellt found in universits laboratories, car-cinogenicity studies can be laige and are verv difficult to do. "Thie numLibers of animllals rcquircd foi a carciniogeniicityx studyv requircd this type of tacility, he saVs. The laboratorv xwas laiunched throhgh an intel agece agreement established ill 1992 betmxeell the NIFHIS an(d the FDA. Other projects currncitlyt fuLnded unlder this agreement inluLide toxicological assessmIcnt of the pediatric acncsthetic chloral hlydrate, the fLuinglal toxin fuimoilsisin BB, the aquLatic fuiigicide mnalachite green, the liquor atnd xvine fermentation products ui-ctlrhane and ethclnol. anid a nutmbeiof endoc--imedisruptinll chcmicals.

The Acid Test for Skin
Ible skin is the largest organ of the humani body and is highly, permeable to xvisible and intfrared light, and partially pernmcable to ULV light, wxhich is knioxxs n to act as a carcinogenl. It was only a decade ago that scientists began to classify corpounlds, especially certain classes of pharmaccutical agents, that could result in increased sensitivity to sunlight iñ m~ NIEHS News someone exposed to them, says Donald Forbes, a researcher at Argus Laboratories in Horsham, Pennsylvania, and an adviser to the National Toxicology Program on the development of the phototoxicology laboratory. In the 1980s, Forbes and fellow dermatologists at Temple University in Philadelphia launched the first phototoxicity tests using simulated sunlight when they tested retinoic acid (Retin-A). Retin-A turned out to be a weak tumor promoter, but Forbes later found that drugs used to treat psoriasis and a new class of very effective oral antibiotics, the fluoroquinolones, produce serious sunburns and rashes in patients. "Drugs like these may be taken internally," says Forbes, "but they flow through the blood to the skin and make living cells at the base of the epidermis much more sensitive to DNA damage." Researchers believe that altering the structure of the skin using creams containing alpha-and beta-hydroxy acids could alter the transmission of some wavelengths of light through the skin. In addition, says Howard, "The skin hates acid. It's buffered to maintain a pH that provides a suitable environment for keratocytes, the predominant skin cell." While natural alpha-hydroxy acids such as those found in fruit are absorbed nicely in the acid-rich environment of the stomach, Howard points out that "we don't normally rub fruit on our skin." There are published data, he says, showing that individuals treated withchemoexfoliants are more susceptible to sunburns. The question, he says iswete the use of these acids~a uMc,,a cancer rates n Soaking in the sun for science's sake. Researchers at a new NTP phototoxicology laboratory are using lamps that simulate sunlight to test for effects of exposures to sun and chemoexfoliants on mice. The results may indicate whether the combination of UV radiation and certain components of beauty products may actually promote skin cancer in humans. so, whether glycolic acid (an alpha-hydroxy foods such as celery and herbal remedies acid) and salicylic acid (the most widely such as St. John's wort both contain chemiused beta-hy,droxy acid) work differently. cals that react to sunlight, and may be studĨ t is hoped that the phototoxicology ied in the future. Says Bucher, "We have an laboratory will answer these questions and obligation to look at naturaltances a others as well. According to John Bucher, well as environmental synthetic chemica project officer for the NIEHS interagency that might 1be pho toot n agreement with the FDA, the laboratory is w h us doki a" Rn6eTwmt designed for testing not only cosmetic chemicals but aso other ioten'Walv pDhoto-