Melanoma model demonstrates damage from early sunburn

By Karla Gale

WESTPORT, CT (Reuters Health) – In transgenic mice that are similar to humans in their susceptibility to melanoma, one skin-reddening exposure to ultraviolet (UV) light during the neonatal period results in tumors in early adulthood, according to a report in the September 20th issue of Nature.

These findings support epidemiological evidence that sunburn during childhood raises the risk of adult melanoma, the research team suggests.

In describing the genesis of the model, Dr. Glenn Merlino told Reuters Health, "Receptor tyrosine kinases have been shown to play a large role in melanomas. Our transgenic mouse carries hepatocyte growth factor, also called scatter factor, which is a ligand that binds to receptor tyrosine kinases." Normally, murine melanocytes are confined to hair follicles, he noted. In the HGF/SF mice, melanocytes are present in the dermis, epidermis, and dermal-epidermal junction.

Dr. Merlino, from the National Cancer Institute in Bethesda, Maryland, and associates of George Washington University Medical School in Washington, DC, exposed 3-day-old albino HGF/SF mice to ultraviolet radiation sufficient to cause skin reddening. Melanoma was induced after "a relatively short latent period and with high cumulative incidence," the investigators write. However, UV irradiation at 6 weeks was not tumorigenic.

"As melanocyte-progenitor cells are more abundant in neonatal than in adult skin and more proliferative under stress, ultraviolet exposure may stimulate proliferation of DNA-damaged neonatal progenitors and thus facilitate melanogenesis," the authors postulate. It is also possible, they suggest, that changes to the immune system caused by UV exposure may promote future tolerance to melanoma.

"We were fortunate in being able to see stages of melanoma," Dr. Merlino commented. "I think the results are striking, in that the cancer looks like human cancer in many ways."

The research group intends to focus on the UV contribution to melanoma. "We'd like to understand whether it is UV-A or UV-B or both that is responsible," Dr. Merlino said. "After that, we can use these mice to devise better sunscreens. We can determine if we can treat the mice prophylactically so that they never develop melanoma. Once they have it, there are many kinds of immunotherapies that can now…be tested in an experimental setting."

Nature 2001;413:271-272.

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