Red-haired individuals prone to melanoma without sunlight exposure, UCR chemists find

Courtesy of Carina Glasser

Chemists at UCR have found that red-haired, fair-skinned individuals contain a skin pigment that may in itself cause the production of UV-independent melanoma. Through experimentation on strains of albino and red-haired mince, findings suggest that the use of sunscreen may not reduce the risk of skin cancer for red-hair individuals.

“We provide a very key piece of evidence to support the central hypothesis,” said UCR chemistry professor Yinsheng Wang, who is working closely with David Fisher of Massachusetts General Hospital on this project. In collaborations with former postdoctoral fellow Jin Wang and graduate Candace Guerrero, Professor Wang is supported by a grant from the National Cancer Institute of the National Institutes of Health.

Both humans and mice contain the skin pigments, pheomelanin and the eumelanin. Through mice experimentation, researchers found that people with the red hair, fair skin phenotypes are more prone to developing the skin cancer, melanoma, due to an excess of pheomelanin. Pheomelanin has a weak-shielding capacity against UV light and induces endogenous formation of reactive oxygen species (ROS). The oxidative damage caused by the ROS is due to its capability to inflict DNA damage, which could result in melanoma.

UCR chemists developed a method to quantitatively assess the oxidative damage done to DNA. Resulting studies reveal that mice with red-hair and fair skin have an increased amount of DNA damage compared to the albino mice even without sunlight exposure. The new findings do not disprove the studies that melanoma form due to UV light, but it is now known that DNA damage can happen with endogenous factors.

In order to quantify the oxidative damage, DNA must first be extracted from the skin tissue of each strand of mice. The DNA then undergoes enzymatic digestion to reduce the DNA strand to single nucleosides. A fixed amount of a 15N isotope labeled nucleoside was used in order to quantify the levels of oxidative DNA damage in skin tissue of each type of mice.

Quantification of each sample is achieved by using a high performance liquid chromatography (HPLC) coupled with mass spectrometry technique, exploiting the ratios between the added standard and the naturally occurring DNA damaged. Ratios from each sample can then be used to quantify the level of oxidative damage DNA based on the initial amount of 15N isotope-labeled standard added. Once each sample is quantified, a comparison was made between different strains of mice. This experiment reveals that oxidative DNA damage, induced by the pheomelanin pigment pathways, is a major factor that drives carcinogenesis in the skin of red-haired, fair-skinned mice.

First-year undergraduate Lucio Garcia Armenta claimed, “It scares me to think that cancer still affects us even though we take care of ourselves by using sunscreen lotion and avoiding the sun [which] makes us extremely vulnerable…”

A paper has been published in Nature on the new findings for mice experimentation. The research project by Wang and his collaborators is aimed towards finding treatments that will prevent melanoma in red-haired, fair-skinned individuals. Right now, the Massachusetts team is accumulating skin specimens to test whether antioxidants will decrease melanoma production in mice and humans.

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