DNA repair is crucial to the integrity of the human genome. The ultraviolet radiation portion of solar radiation is responsible for the rising incidence of skin cancer, one of the most common types of cancer in humans. We applied a recently developed 32P-postlabeling technique to measure the in situ DNA repair efficiency of solar-simulated radiation induced cyclobutane pyrimidine dimers and 6-4 photoproducts in the skin of nine healthy volunteers with skin type II. Our results show about 6-fold interindividual variations in the level of DNA damage after exposure to an equal biologic dose - 2 minimal erythema doses. The kinetics of DNA repair indicated a base sequence dependence of the repair process. The DNA repair efficiency showed a 20-fold difference in volunteers. An age-related decrease of DNA repair capacity was observed; however, the data are limited due to a small number of subjects and a narrow age range. The variable response in DNA damage levels and individual differences in DNA repair efficiency suggest a susceptible subgroup of people probably with a higher skin cancer risk.

Sunscreens prevent sunburn and may also prevent skin cancer by protecting from ultraviolet-induced DNA damage. We assessed the ability of two sunscreens, with different spectral profiles, to inhibit DNA photodamage in human epidermis in situ. One formulation contained the established ultraviolet B filter octyl methoxycinnamate, whereas the other contained terephthalylidene dicamphor sulfonic acid, a new ultraviolet A filter. Both formulations had sun protection factors of 4 when assessed with solar simulating radiation in volunteers of skin type I/II. We tested the hypothesis that sun protection factors would indicate the level of protection against DNA photodamage. Thus, we exposed sunscreen-treated sites to four times the minimal erythema dose of solar simulating radiation, whereas vehicle and control sites were exposed to one minimal erythema dose. We used monoclonal antibodies against thymine dimers and 6-4 photoproducts and image analysis to quantify DNA damage in skin sections. A dose of four times the minimal erythema dose, with either sunscreen, resulted in comparable levels of thymine dimers and 6-4 photoproducts to one minimal erythema dose +/- vehicle, providing evidence that the DNA protection factor is comparable to the sun protection factor. The lack of difference between the sunscreens indicates similar action spectra for erythema and DNA photodamage and that erythema is a clinical surrogate for DNA photodamage that may lead to skin cancer.

We have investigated the photoprotective properties of tanning using erythema as an endpoint. Previously unexposed buttock skin sites of 16 young, healthy adults (8 skin type II, and 8 skin type III) were exposed daily (Mon-Fri) for 2 weeks to 0.5 and 0.75 minimal erythema doses (MED) of solar-simulated radiation (SSR). Erythema and melanin levels were assessed daily both visually and quantitatively using a reflectance device. One week after the last tanning treatment, MED reassessments were made on pretreated sites and on adjacent nontreated sites, including sites from which stratum corneum was removed by tape stripping. Compared to skin type II, similar daily SSR treatments produced less erythema and more evident tanning in skin types III. Independent of skin type, all volunteers showed an increased MED value when assessed on the 0.75 MED- and 0.5 MED-treated sites compared to the MED value assessed on adjacent untreated sites. We express any increase in MED as an induced protection factor (IPF), i.e. (MED post-tan/MED pre-tan). Our data show mean IPF of 1.4 and of 2.1 in the 0.5 and 0.75 MED-treated sites respectively, in skin types II. Similar values were obtained in skin types III with IPF of 1.5 and 2.3 for the 0.5 and 0.75 MED-treated sites, respectively. In all cases, removal of the stratum corneum lowered the IPF by about 20%. Our results show that SSR-induced melanogenesis, whether in skin type II or III, offers only moderate protection against erythema and suggest that SSR-induced stratum corneum thickening affords less photoprotection than tanning.

The sunburn cell (SBC), with its pyknotic nucleus and eosinophilic cytoplasm, is characteristic of mammalian epidermis after exposure to UVC and UVB radiation or UVA radiation in the presence of psoralens. SBC may be regarded as an example of apoptosis: controlled individual cell death. Since the discovery of apoptosis over thirty years ago, there has been a considerable increase in the knowledge of mechanisms involved in this process. DNA damage has been shown to be a major determinant of SBC production both in a p53-dependent and -independent manner. Extranuclear events such as activation of membrane bound death receptors also contribute to SBC formation. The development of new technologies and techniques has resulted in a better understanding of the mechanisms and machinery involved in apoptosis, triggered by various stimuli and in different cell types. Of particular importance has been the elucidation of regulatory molecules such as caspases, inhibitor of apoptosis proteins (IAP) and the role of mitochondria as key to the process of apoptosis and consequent production of SBC. This review attempts to give an update on those mechanisms involved and the occurrence and relevance of SBC in mammalian skin are discussed.