National report — Redheads are much more sensitive to sunburn and are more prone to developing skin cancer, even when they don't burn. Why is that? What is the biological mechanism of action that makes all of this happen?
Those questions would launch Duke University biochemist John Simon, Ph.D., on a path that would take more than seven years, new methodologies and unanticipated collaborations to answer.
He focused on sunlight and the electro-chemical effect it has on melanin, a pigment produced in skin, hair and the retina of eyes.
The first task was to obtain sufficient melanin to examine. Skin melanosomes - intact granules of melanin - lose their shape and flatten out along the more exposed side of the cell wall of keratinocytes.
"Hair melanosomes offered the cleanest and purest separations of the two different-colored pigments. There is black pigment in red, but there isn't any red in black," Dr. Simon explains.
Earlier processes for removing intact melanosomes from hair degraded the chemical integrity of the pigment, but in 2000, an Italian researcher developed a novel method for extracting melanosomes from hair without such degradation. It then became possible to obtain good samples of melanosomes.
The next step was to use a tunable laser to expose the samples to a variety of UV wavelengths found in natural sunlight. The longer-wavelength UVB portion of the spectrum is associated with surface tanning, sunburns and cellular damage, while the shorter UVA wavelengths can penetrate deeper into layers of the skin, damaging cells without evidence of sunburn.
He measured the electrons or free radicals generated by that exposure using a photoelectric emission microscope. Free radicals and associated oxidation are a significant source of damage to cellular DNA that can contribute to the development of cancer.
He found that the entire UV spectrum could activate pheomelanin, the red pigments, along a dose response curve and cause them to lose electrons. Black pigments - eumelanin - would lose electrons only when exposed to the longer-wavelength UVB portion of the spectrum. And those rays are more likely to be blocked by clouds and dust particles.
"The red pigment is more pro-oxidant under normal atmospheric UV exposure and more prone to cause oxidative stress in cells," Dr. Simon says. "This suggests that the photochemical properties of the pigments themselves may contribute to the different incidence of cancer between tissues containing the different pigments."
He says the findings don't offer any easy or direct link to a new therapeutic approach to treating exposure to toxic levels of sunlight. But they do reinforce the importance of using sunscreen and other techniques to avoid such damage in the first place, particularly for those with fair skin.
The research was first presented at the 230th national meeting of the American Chemical Society, in Washington, at the end of the summer.