UV Blocker: Lotion yields protective tan in fair-skinned mice
Nathan Seppa
A lotion that stimulates production of the skin pigment melanin induces a deep tan in specially bred laboratory mice. Those mice have skin similar to that of red-headed, fair-skinned people, who are notoriously poor tanners.
The animals developed their tans without being exposed to the sun and its ultraviolet (UV) rays. Further tests showed that the additional melanin protected the mice against UV-induced DNA damage, sunburn, and skin cancer.
The active ingredient in the lotion is forskolin, an Asian plant extract that has been used to treat health problems. But scientific studies of the compound in the past few decades have shown no clear benefit, says study coauthor David E. Fisher, an oncologist at the Dana-Farber Cancer Institute and Children's Hospital in Boston. Nevertheless, past tests had shown that forskolin can rev up production of cyclic AMP, a molecule that's instrumental in producing melanin.
Normally, melanin manufacture requires several steps. When sunlight's UV rays hit the skin, cells release a signaling compound that binds to proteins on the surface of melanocytes, the cells that make melanin. This docking activates cyclic AMP production inside the melanocyte, which spurs the cell to make melanin and distribute it to nearby skin cells.
There, melanin forms an array of microscopic parasols over the skin cells' nuclei, shielding the DNA from ultraviolet rays. The melanin darkens the cell and reduces burn risk.
In the new study, Fisher and his team used mice that, like red-headed people, have surface proteins on their melanocytes that are poor docking stations for the signaling compound. That interrupts melanin production.
Mice coated with the forskolin lotion for 3 weeks made more melanin and became dramatically darker than mice getting a neutral lotion.
Untreated mice exposed to UV rays for 24 hours had more than 20 times as much DNA damage and sunburn as did mice that had been treated with forskolin. After 20 weeks of exposure to UV rays for an hour or so each day, untreated mice developed nearly twice as many skin tumors as did the treated mice, the scientists report in the Sept. 21 Nature.
The results show that "the reduced DNA damage has a [positive] biological consequence," says molecular biologist Richard A. Sturm of the University of Queensland in Brisbane, Australia. Increased melanin reduced death among skin cells.
Studies had previously established that people with dark skin are less likely to become sunburned or get skin cancer than fair-skinned people are. With the new work, Sturm says, Fisher and his team "display the tangible proof ... for a photo-protective role of melanin."
Sturm is cautious about the possibility of providing people with a forskolin-containing cream. He notes that cyclic AMP can stimulate cell growth, so increased amounts of that molecule might pose a cancer risk.
Fisher is cautious too. "I am far from certain [that such a cream] would have activity in human skin," he says. Still, the findings suggest that intervening in the melanin-production process has potential as a cancer preventive, he says.
"If [forskolin] turns out to be safe and acceptable for human use, it can only be helpful," says dermatologist Barbara A. Gilchrest of Boston University School of Medicine.
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References:
D'Orazio, J.A. . . . and D.E. Fisher. 2006. Topical drug rescue strategy and skin protection based on the role of Mc1R in UV-induced tanning. Nature 443(Sept. 21):340-344. Abstract available at http://dx.doi.org/10.1038/nature05098.
Further Readings:
Aberdam, E. . . . D.E. Fisher, et al. 1998. Involvement of microphthalmia in the inhibition of melanocyte lineage differentiation and of melanogenesis by agouti signal protein. Journal of Biological Chemistry 273(July 31):19560-18565. Available at http://www.jbc.org/cgi/content/full/273/31/19560.
Beaumont, K.A. . . . and R.A. Sturm. 2005. Altered cell surface expression of human MC1R variant receptor alleles associated with red hair and skin cancer risk. Human Molecular Genetics 14(June):2145-2154. Available at http://hmg.oxfordjournals.org/cgi/content/full/14/15/2145.
Rees, J.L. 2004. The genetics of sun sensitivity in humans. American Journal of Human Genetics 75(November):739-751. Available at http://www.journals.uchicago.edu/AJHG/journal/issues/
v75n5/41493/41493.html.
Schwahn, D.J., et al. 2001. Tyrosine levels regulate the melanogenic response to alpha-melanocyte-stimulating hormone in human melanocytes: Implications for pigmentation and proliferation. Pigment Cell Research 14(February):32-39. Abstract available at http://dx.doi.org/10.1034/j.1600-0749.2001.140106.x.
Thody, A.J. 1999. a-MSH and the regulation of melanocyte function. Annals of the New York Academy of Sciences 885(October):217-229. Abstract available at http://www.annalsnyas.org/cgi/content/abstract/885/1/217.
Valverde, P., et al. 1995. Variants of the melanocyte-stimulating hormone receptor gene are associated with red hair and fair skin in humans. Nature Genetics 11(November):328-330. Abstract available at http://dx.doi.org/10.1038/ng1195-328.
Valverde, P., et al. 1995. Melanin pigmentation plays an essential role in protecting the skin from the damaging effects of ultraviolet radiation (UVR). 6th Meeting of the ESPCR. Lausanne, Switzerland. October. Abstract available at http://www.ulb.ac.be/medecine/loce/espcr/b_iss/Dis-24a.htm.
Sources:
David E. Fisher
Department of Pediatric Hematology/Oncology
Dana-Farber Cancer Institute and Children's Hospital
44 Binney Street
Boston, MA 02115
Barbara A. Gilchrest
Boston University
School of Medicine
609 Alban Street
Boston, MA 02118
Richard A. Sturm
Melanogenix Group
Institute for Molecular Bioscience
Level 3 North
Queensland Bioscience Precinct
University of Queensland
Brisbane, Queensland 4072
Australia
From Science News, Volume 170, No. 13, September 23, 2006, p. 196.
