Inhibition of solar simulator-induced p53 mutations and protection against skin cancer development in mice by sunscreens.

We demonstrated previously that p53 mutations can be detected in ultraviolet B-irradiated mouse skin months before the gross appearance of skin tumors and that applying sun protection factor 15 sunscreens to mouse skin before each Kodacel-filtered FS40 sunlamp irradiation resulted in the reduction of such mutations. To determine whether there is an association between reduction of ultraviolet-induced p53 mutations by sunscreens and protection against skin cancer using an environmentally relevant light source, we applied sunscreens (sun protection factors 15-22) on to the shaved dorsal skin of C3H mice 30 min before each exposure to 4.54 kJ ultraviolet B (290-400 nm) radiation per m2 from a solar simulator. Control mice were treated 5 d per wk with ultraviolet only or vehicle plus ultraviolet. p53 mutation analysis indicated that mice exposed to ultraviolet only or vehicle plus ultraviolet for 16 wk (cumulative exposure to 359 kJ ultraviolet B per m2) developed p53 mutations at a frequency of 56%-69%, respectively, but less than 5% of mice treated with sunscreens plus ultraviolet showed evidence of p53 mutations. More importantly, 100% of mice that received a cumulative dose of 1000 kJ ultraviolet B per m2 only, or vehicle plus ultraviolet B developed skin tumors, whereas, the probability of tumor development in all the mice treated with the sunscreens plus 1000 kJ ultraviolet B per m2 was 2% and mice treated with sunscreens plus 1500 kJ ultraviolet B per m2 was 15%. These results demonstrate that the sunscreens used in this study not only protect mice against ultraviolet-induced p53 mutations, but also against skin cancers induced with solar-simulated ultraviolet. Because of this association, we conclude that inhibition of p53 mutations is a useful early biologic endpoint of photoprotection against an important initiating event in ultraviolet carcinogenesis.

Erythema induction by ultraviolet radiation points to a possible acquired defense mechanism in chronically sun-exposed human skin.

BACKGROUND: It is generally accepted that a UVA-induced erythema is difficult to detect except in the most sensitive individuals. OBJECTIVE AND METHODS: As UVA effects on human skin and skin cells have been shown to depend strongly on anatomical body sites, UVA I, UVA I + II and solar simulator radiations were compared in their ability to induce erythema and melanin pigmentation responses in individuals with skin types I-IV on both previously sun-exposed (arms, forearms, thighs) and nonexposed body sites (buttocks). RESULTS: Erythema induction by UVA I on previously nonexposed skin sites followed a dose response in all skin types which was contrary to the absence of erythema induction seen on previously sun-exposed sites. Melanin expression followed a dose and skin type response and was shown to be more enhanced in previously exposed skin and in skin types III and IV. In contrast, UVA I + II induced erythema on nonexposed skin areas and to a lesser extent on frequently sun-exposed skin. Melanin production by UVA I + II was similar to that seen with UVA I alone in individuals of skin types II and III. Solar simulator radiation was very efficient in erythema induction regardless of previous sun exposure of skin. CONCLUSIONS: We have found that contrary to the widespread opinion that UVA and in particular UVA I could not induce a significant erythema, this waveband is capable of measurable erythema induction on skin nonexposed to sunlight. The diminished erythema induction by UVA I on chronically sun-exposed skin suggests the possibility of a defense mechanism against UVA-induced damage in this tissue.

Proposed protocol for determination of photostability Part I: cosmetic UV filters.

Synopsis The protocol described here has been developed to measure the stability of UV-B filters; a modified version is recommended for UV-A filters. It should be considered as a tool to predict the effectiveness remaining after exposure to UV-A and UV-B light. It is a simple and reliable in vitro model simulating conditions of actual use. The results show that each filter requires an appropriate choice and fine tuning of reproducible analytical conditions. While absolute values are directly influenced by uncertainties in irradiance (dosimetry), comparative measurements with respect to a known standard are very reliable.