Lotion speeds DNA repair, protects mice from skin cancer.

It's not always fun in the sun. Dermatologists warn that not even the best sunscreens prevent all the potentially cancer-causing damage that ultraviolet light (UV) does to skin. A new study, however, suggests that incorporating certain snippets of DNA into sunscreens could prompt skin to repair UV-induced genetic damage before it leads to cancer. Indeed, scientists have found that slathering such DNA fragments onto UV-exposed hairless mice thwarts skin cancer.

The investigators speculate that the DNA bits mimic chromosome damage in the skin cells that pick them up, and thereby tell the cells to boost their DNA-repair activity. "We think we've tapped into a very important signaling pathway," says Barbara Gilchrest of Boston University School of Medicine.

When ultraviolet light hits an unprotected skin cell, it can damage the cell's DNA. That may lead to a long-lasting mutation, if the cell doesn't quickly repair the molecular lesions.

Tanning is another way the skin protects its cells from the sun: The pigment melanin helps skin cells more safely absorb ultraviolet radiation.

In 1994, Gilchrest and her colleagues reported that applying a specific tiny snippet of DNA to human skin ceils or the skin of guinea pigs induces a tanning response. The snippet, known as thymidine dinucleotide (pTT), consists of just two nucleotides, the basic building blocks of DNA. In 1997, Gilchrest and her colleagues reported that pTT also prompts cells to quicken their repairs of DNA damage caused by ultraviolet light.

In the latest research, Gilchrest, her Boston colleague David A. Goukassian, and their coworkers found that hairless mice swabbed with a solution containing pTT developed 38 percent fewer UV-induced mutations in their DNA than did rodents not getting the pTT treatment.

In another rodent experiment, the researchers for 6 months alternated 1 week of daily treatments with pTT with 3 weeks of daily UV light exposure. Among untreated rodents receiving the same UV exposure, some began to develop skin lesions as early as 9 weeks into the study, and 88 percent of the animals had tumors by the end, Goukassian and his colleagues report in a forthcoming Proceedings of the National Academic of Sciences. In pTT-treated animals, the first tumors didn't appear until the study's 16th week, and only 22 percent of the animals had tumors at the end of the study.

The researchers would now like to team up with others to conduct pTT studies on people.

"If these data are supported and confirmed by other researchers, it certainly is promising that [pTT] could function to prevent the development of skin cancer," says dermatologist David Leffell of Yale University.

Gilchrest, Goukassian, and their colleagues found that pTT isn't the only DNA snippet that boosts a skin cell's DNA-repair activity. Any short stretch of nucleotides does the trick if it resembles a portion of the 6-nucleotide sequence making up a telomere, the DNA that protects chromosomes' integrity by capping their ends. The researchers speculate that adding pTT to a call fools it into thinking telomeres are damaged, leading to the production of DNA-repair enzymes.

Telomere biologists remain skeptical. "If the application of pTT affects some aspect of telomere biology, this would be very exciting, but more work needs to be done to establish the underlying mechanism of pTT

protection," says Titia de Lange of Rockefeller University in New York.