Benzothiazole carboxylic acid (BTCA) vs thiazole carboxylic acid (TTCA) as specific pheomelanin markers: relationship with skin phototype and UV sensitivity

Pigmentary traits such as red hair, fair skin and the lack of tanning ability are generally recognized as risk factors for melanoma and other skin cancers. However different response to UV exposure are observed among individuals exhibiting similar phenotypes. The association between loss of function mutations at the melanocortin-1 receptor (MC1R) and high risk red hair phenotypes has now been firmly established but a relationship of such genetic traits and the type and amounts of cutaneous melanins have not so far been extensively investigated, nor has the presence of pheomelanins, the typical red hair pigments, been assessed in those individuals bearing the most common allelic variants. We reported that pheomelanic tissues may be identified by analysis of two highly specific structural markers namely 1,3-thiazole-2,4,5-tricarboxylic acid (TTCA) and 6-(2-amino-2-carboxyethyl)-2-carboxy-4-hydroxybenzothiazole (BTCA) obtained by chemical degradation of the pigments. Most of the red human hair examined showing different hues afforded TTCA in variable yields, while BTCA was obtained only from a restricted number of samples. BTCA positive individuals exhibited a marked tendency to actinic damage as evidenced by MED values. These preliminary data have now been confirmed on a larger group of red haired individuals. The lowest MED values and 5-days delayed pigmentation was associated with BTCA-positive subjects while TTCA-positive subjects gave statistically significant higher MED values. The potential of pheomelanin markers associated with determination of photobiogical parameters and quantitation of other metabolic markers for predicting individuals at high risk for skin cancer and melanoma in large populations will be discussed.