632 Photoprotection by constitutive melanin: Correlating deoxyribonucleic acid damage in vivo and skin cancer incidence

Ultraviolet radiation (UVR) causes DNA damage, which initiates skin carcinogenesis. Epidemiological studies show a lower skin cancer incidence in people with dark skin compared to fair skin. This is attributed to photoprotection by epidermal melanin. Some authors have shown that the degree of UVR-induced DNA damage is influenced by constitutive pigmentation with greater protection (maximum of 7 fold) afforded by dark skin. We have studied how a skin cancer biomarker differs in Caucasian (Skin phototype (SPT) I/II) and West African (SPT VI) subjects. Upper buttocks of subjects (6 SPT I/II, 6 SPT VI) were exposed to a dose series of solar simulated radiation (SSR). Exposures were based on standard erythema doses (SED). The SED range for a given SPT was based on minimal erythema dose (MED) because the MED of SPT VI is ∼10 times higher than SPT I/II. Biopsies were taken immediately after exposure, sectioned and stained with a monoclonal antibody against cyclobutane pyrimidine dimers (CPD). We found a comparable amount of CPD in the overall epidermis, in each SPT group, when the SSR dose in SPT VI is 10 fold greater than in SPT I/II, thus indicating an overall melanin DNA protection of 10. These results suggest that UVR-induced CPD in the whole epidermis is linked to the erythema response. Comparisons at different epidermal zones (upper, mid, basal) showed that unlike SPTI/II, SPT VI showed a clear effect of epidermal zone with fewer CPD with increasing epidermal depth. The basal layer contains proliferative stem cells thus lesions here may be relevant to greater susceptibility to skin cancer. The protective effect of melanin in the basal layer was about 40 fold; a figure close to the 32 fold difference in melanoma incidence in dark and fair individuals. Our data stress the importance of the localisation of epidermal biomarkers for skin cancer that has been largely ignored in previous studies.