Chemical effects of pigmentation variation

2 minute read

I lectured on pigmentation in my introductory class this week, and this recent news story is relevant: “Redheads may be at higher risk of melanoma even without sun”. The article describes experiments in which mice were kept out of UV radiation entirely for the control portion of another experiment, when the researchers noticed a clear difference:

When researchers compared skin samples of the different mice, the redheaded mice showed almost three times as much damage due to oxidative stress, leading authors to conclude that pheomelanin was the culprit.
Conversely, the brown-black pigment, eumelanin, possibly acted as an antioxidant in the black-haired mice and counteracted the red pigment's damaging behavior. The albino mice lacked either type of functioning pigment.

The genetic pathway underlying pigmentation is fairly well understood, but there are still unknown biochemical aspects of these molecules, which are locally quite concentrated in some tissues. The research described here was in Nature recently, by Devarati Mitra and colleagues Mitra:melanoma:2012. The conclusion of that paper reflects on the implications for understanding human pigmentation variation:

Further evidence suggesting an ultraviolet-radiation-independent red hair/fair skin melanoma risk is the observation that although darker-skinned individuals have a significantly lower risk of melanoma than lighter-skinned individuals, the sun protective factor (SPF, a measurement of sunburn protection) of darker skin has been estimated at only in the range of SPF 2.04.0 (ref. 28). In addition, sunscreen (typically SPF 2040) has shown weak efficacy in protecting against melanoma, unlike its protection against cutaneous squamous cell carcinoma. There are numerous potential explanations for the sunscreen-melanoma data including the possibility that ultraviolet radiation shielding may protect against only one of several carcinogenic mechanismswith the intrinsic pheomelanin pathway representing an additional contributor to melanomagenesis via ultraviolet-radiation-independent means. These data are not evidence against a role for ultraviolet radiation in melanomagenesis. Indeed, the effect of ultraviolet radiation is likely to exacerbate this mechanism, such that ultraviolet radiation shielding and sunscreen remain extremely important for skin cancer prevention. However, further preventative strategies may be essential to optimally diminish melanoma risk in the most susceptible individuals.

Most teachers who present human pigmentation as a defense against UV radiation gloss over the relatively low SPF of darker skin. That’s not to say it isn’t helpful in reducing UV-induced damage, but it’s not a perfect defense. In case you wonder why most juvenile humans retain hair covering for their heads, that low SPF protection from melanin is part of the explanation.