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

We demonstrated previously that p53 mutations can be detected in ultraviole t 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 o f such mutations. To determine whether there is an association between redu ction of ultraviolet-induced p53 mutations by sunscreens and protection aga inst 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 m(2) from a solar simulator. Control mice were treated 5 d pe r wk with ultraviolet only or vehicle plus ultraviolet, p53 mutation analys is indicated that mice exposed to ultraviolet only or vehicle plus ultravio let for 16 wk (cumulative exposure to 359 kJ ultraviolet B per m(2)) develo ped p53 mutations at a frequency of 56%-69%, respectively, but less than 5% of mice treated with sunscreens plus ultraviolet showed evidence of p53 mu tations. More importantly, 100% of mice that received a cumulative dose of 1000 kJ ultraviolet B per m(2) only, or vehicle plus ultraviolet B develope d skin tumors, whereas, the probability of tumor development in all the mic e treated with the sunscreens plus 1000 kJ ultraviolet B per m(2) was 2% an d mice treated with sunscreens plus 1500 kJ ultraviolet B per m(2) was 15%. These results demonstrate that the sunscreens used in this study not only protect mice against ultraviolet-induced p53 mutations, but also against sk in cancers induced with solar-simulated ultraviolet. Because of this associ ation, we conclude that inhibition of p53 mutations is a useful early biolo gic endpoint of photoprotection against an important initiating event in ul traviolet carcinogenesis.