Chemical markers of pheomelanin : evaluation of their potential of predicting individual UV susceptibility

Red hair, fair skin and the lack of tanning ability are generally recognized as risk factors for melanoma and other skin cancers under conditions of prolonged solar exposure. These pigmentary traits are associated with some loss of function mutations at the melanocortin-1 receptor which cause the melanocyte to produce red photosensitizing pheomelanin in preference to the default pigment, the dark eumelanin. At present evaluation of UV susceptibility relies exclusively on determination of the phenotype and phototype. Yet, not all phenotypically similar red haired individuals exhibit the same erythemogenic responses and tanning capacities, suggesting that the type and levels of pheomelanin may profoundly affect the individual response to UV radiation. Identification of specific markers of pheomelanin pigments and determination of possible relationships with skin phototypes and UV susceptibility appear therefore attractive goals. Recently we developed new procedures for analysis of pheomelanin based on identification and quantitation of specific structural markers obtained by chemical degradation of hair. The levels of these structural markers , viz.1,3-thiazole-2,4,5-tricarboxylic acid (TTCA) and 6-(2-amino-2-carboxyethyl)-2-carboxy-4-hydroxybenzothiazole (BTCA) were determined in groups of red hair individuals. Whereas the majority of the red hair samples afforded TTCA in variable yields, only a restricted number of samples gave BTCA. Herein, we report new data from a larger group of red haired individuals (n=22). As a rule, the lowest MED and 5-days delayed pigmentation values were associated with BTCA-positive individuals while TTCA-positive subjects gave higher MED values (mean value 67.5 mJ cm-2, p< 0.001). Overall, these results hint at pheomelanin marker quantitation, in combination with genetic analysis and photobiogical parameters, as potential means for routine prediction of high risk individuals. A possible association of oxidative stress conditions with pheomelanic pigmentation will also be discussed.