Sunburn and mechanisms of protection 39 The carcinogenic action of uvr appears to derive from both the mutagenic effects and the hyperplasia inducing action. The uvr wavelength region involved is basically similar to that for uv-erythema but may well differ in detail and there is little reason to suppose that the mechanisms involved in uvr carcinogenesis are simply those in uv-erythema pro- duetion repeated over a long term. PROTECTION The endogenous mechanisms for protection against the effects of uvr on sktn may operate in three distinct ways. In the first place, uvr damage in the skin may be rapidly repaired: the lack of repair is held responsible for the increased sensitivity seen in Xeroderma Pig- mentosum. Secondly, physiological processes may be present by which the energy of excited state molecules or the reactive oxidation products of uv-irradiation may be quenched or harmlessly dissipated. Natural anti-oxidants such as alpha-tocopherol may act in this way. However, the natural carotenoids do not appear to be effective in the normal sunburn reaction (94). The third and most obvious mechanism involves the attenuation of the incident radiation between the skin surface and the molecular target in the skin. HORNY LAYER In lightly pigmented skin, the major contribution to this attenuation comes from the horny layer of the epidermis. The multi-faceted surfaces present in this dead cell layer produce considerable reflection and scattering and the dense protein content provides a filtering effect by absorption. The importance of this attenuation is demonstrated by the difficulty experienced in producing uv-erythema in palmar or plantar skin, by the in- crease in intensity of erythema obtained in skin from which the horny layer has been removed, and by the fact that in the amelanotic skin of Vitiligo and Albinism thickening of the horny layer affords some protection against uvr damage. Bachem (23) showed that only some 15•o of incident 280-nm radiation penetrated a 0.08-mm thickness of fair- skinned horny layer. At 300 nm, a value of 34•o was obtained, while 80•o of 400-nm radiation penetrated to the Malpighian layer. These results are typical of many obtained in studies designed to assess the protective function of the horny layer or to determine the anatomical site of uvr action in skin. Miescher (95) showed that the penetration of 297-320 nm radiation could be described as an exponential extinction with a half-value layer of about 9 microns. UROCANIC ACID The role of urocanic acid as a natural sunscreen for human skin remains debatable (96, 97, 98, 99, 100). This metabolite of histidine, found in human sweat and at higher con- centrations in the epidermis, has an absorption spectrum which extends into the sunburn uvr. In unexposed skin, it is present mostly in the cis form, uv-irradiation resulting in a cis-trans isomerisation. It is this isomerisation with the absorbed energy being dissipated in the reverse direction which may account for any protective role ascribed. The urocanic acid content of epidermis in skin which has been previously exposed to uvr and shows a decreased sensitivity through accommodation, is found to be increased and it may be that the contribution of this protective mechanism to the overall decrease in sensitivity

40 B. E. Johnson of accommodated skin is greater than that of the protein constituents of the horny layer. MELANIN The major contributory factor in the natural protection of human skin against uvr is the complex, indole type polymer called melanin. The relationship between sunlight and melanin pigmentation has been most recently reviewed by Pathak et al. (9), and Quevedo et al. (101), Szabo (102), and Pathak (103) present good coverage of the subject matter as known at that time. The development of a suntan in normally lightly pigmented skin, resulting from a uvr-stimulated redistribution of preformed melanosomes in the epi- dermis and the tyrosinase controlled production of melanised melanosomes in the melanocytes with subsequent transfer to and distribution in the keratinocytes of the hyperplastic epidermis, obviously affords protection against further uvr exposure. The genetically controlled variation in number, form and distribution of melanosomes, mainly responsible for racial variation in skin colour, results also in variations in the skin responses to uvr. In fair-skinned Celtic peoples, Albinos and in vitiliginous skin, where little or no melanin is present, the skin reactions are severe. As the degree of melanisation increases, so the intensity of skin reactions decreases and in deeply pig- mented Negroids and Australoids, it is difficult to elicit reactions other than the IPD and skin cancer due to uvr does not occur. It is thought that the racial variation in human skin colour may represent an evolutionary compromise between the need to protect against the carcinogenic action of uvr and the requirement of photochemically-produced vitamin D in the viable layers of the epidermis (104, 105). The transmission of 280-320 nm radiation through negro horny layer is significantly less than through that from white skin, but there is no significant difference in the thickness of this layer (106, 107). The only difference appears to be the presence of melanin as demonstrated by Kligman (108). The mechanisms by which melanin exerts its protective function apparently vary. It may act as a neutral density filter in the outermost layers of the epidermis where it is present in a disperse, amorphous form. The absorbed energy is dissipated harmlessly as heat. Moreover, in this form it acts as an excellent scattering screen for the wavelengths involved. The scattering produced by the larger melanin granules, usually observed in a supranuclear distribution in the basal and suprabasal layers, is thought to involve a high degree of forward direction, and if this is so the function of the superanuclear caps in protecting the germinal DNA is a little difficult to accept. Stable free radicals are present in the melanin polymer and may act as electron traps in a uvr-excited system. However, the spatial relationship between the potentially susceptible biological substrate, for instance DNA, and the melanin would have to be rather more intimate than it appears in electron microscope pictures for this protective mechanism to function efficiently. It is also thought that melanin may act as a semi-conductor material, in this way diverting electron energy away from susceptible biological material. The exact mechanisms involved in melanin protection against uvr damage, apart from the action as a filter, are obviously not as yet worked out, but it would seem that they do exist and are effective. CONCLUSION In summary, the reactions of human skin to the uvr component of solar radiation may vary according to the intensity and wavelength of the incident radiation from the mildest