摘要
Sun exposure is responsible for deleterious effects such as sunburn, photoaging, and skin cancer. Ethnic origin and skin color, related to constitutive pigmentation represent major parameters involved in skin responses to solar ultraviolet (UV) exposure. Epidemiologic studies show higher incidences of basal and squamous cell carcinoma as well as melanoma in Caucasians compared with African Americans.1 Skin susceptibility to photoaging alterations such as solar elastosis, dermal damage, and wrinkle formation, also depends on constitutive pigmentation. Furthermore, experimental data show the relationship between the minimal erythemal dose (MED) and skin color (i.e., MED is lower in light skin and higher in dark skin).2 The skin color type is usually assessed according to Fitzpatrick’s phototype classification, which is based on ethnic origin, erythema sensitivity, and tanning ability. Nevertheless, this classification may raise various problems such as limits in terms of quantification, reliability, and ex vivo conditions. In addition, its relevance for Asiatic or African skin types has been questioned as all Asian skin types were grouped into a unique phototype V and all African skins in phototype VI. To document the relationship between the response to UV light and skin color type, we analyzed 42 ex vivo skin samples. Skin color type was determined through the measurement of the individual typology angle (ITA), which is based on colorimetric parameters.4 This allowed us to objectively classify the skins into five groups, namely light, intermediate, tanned, brown, and dark. Skin color classification according to ITA was checked with regard to physiological relevance to constitutive pigmentation by Fontana–Masson staining, revealing clear differences in melanin content and distribution regardless of ethnic origin. Colorimetric parameters obtained from African women living in France and the USA showed that African skins were distributed from intermediate to dark skin type (Fig. 1). African skin colorimetric classification in the skin color volume projected on the L*/b* plane of the L*a*b* space (CIE 19763). The vertical axis L* is the luminance or lightness of the skin and the horizontal axis b* is the yellow component of the skin. Skin color categories from very light to dark are indicated As a biological end-point of the MED, which corresponds to just perceptible erythema, we analyzed the number of sunburn cells (SBC) 24 h after exposure to increasing doses of solar-simulated radiation (UVB + UVA). This led to determination of the biologically efficient dose (BED) for each sample. We found a dose-dependent SBC induction in all skin color types. More interestingly our results revealed a direct relationship between skin color type and BED value, with a statistically significant correlation between ITA and BED (i.e., the lighter the skin the lower the BED value) (Fig. 2). Other typical biological markers are associated with erythemal reaction and have been linked to the development of skin cancer, such as DNA lesions and p53 accumulation. The latter markers were evaluated and, as found with SBC, showed a correlation between the value of ITA and dose-inducing biological damage. Interestingly, immunolabeling of cyclobutane pyrimidine dimers, a major UV DNA damage in human skin, showed dose-dependent accumulation of lesions throughout the epidermal layers and uppermost dermal cells in light, intermediate, and tanned skin. In contrast, cyclobutane pyrimidine dimers could not be detected in the basal epidermal layer and dermal cells of brown and dark skins (Fig. 3). They were strictly restricted to suprabasal epidermal keratinocytes, even when exposed to doses greater than the BED. To investigate the greater resistance of dark skin to UV exposure, three different dark skin samples were collected and exposed to high UV doses corresponding to two- or threefold the average BED for this skin type. Surprisingly, no pyrimidine dimers were detected in the basal layer of the epidermis and in the upper dermis. Individual typology angle (ITA°) versus biologically efficient dose (BED): linear regression (R2 = 0.70; P < 0.001). Corresponding skin color types are indicated. Int, intermediate Fontana–Masson staining: one example of each skin type is illustrated and corresponding ITA values are indicated. Immunolabeling of CPD immediately SSR exposure: one example of each skin type is illustrated before exposure (0 J/cm2) and at the BED (in J/cm2). Broken line indicates the dermal–epidermal junction. Small arrows point to dermal positive cells. Vertical arrows indicate the depth of staining. Circles surround the basal layer of brown and dark skins where no CPD was detected. BED, biologically efficient dose; CPD, cyclopyrimidine dimers; ITA, individual typology angle. Altogether, from a biological point of view, our results show a decreasing UV sensitivity from light to dark skin.5 The different distribution of DNA lesions between ITA-based groups supports the relationship between UV sensitivity and skin color type at the molecular level. The location of DNA lesions in the epidermis is of utmost importance with regards to the onset of skin carcinogenesis. DNA lesions in suprabasal keratinocytes committed to terminal differentiation do not carry the same biological impact as lesions in the basal proliferative layer highly suspected to be at the origin of epidermal carcinoma development. These results may explain the lower risk of darker skin to develop UV-induced skin cancer. Furthermore, the presence of DNA lesions in the upper dermis of light skin may be relevant to greater susceptibility to dermal damage related to photoaging. Skin color classification based on ITA values seems to be related to skin sensitivity to UV exposure at the cellular and molecular levels. Our results indicate a progressive decrease in sensitivity to UV exposure with increasing skin pigmentation. This sensitivity is likely to be predictive of the individual proneness to develop deleterious consequences of sun exposure, photoaging, and skin cancer. We believe that the determination of ITA may be a useful tool to predict individual “UV exposure risk” profiles for designing adequate photoprotection or skin cancer prevention programs.