Effects of sunscreens and a DNA excision repair enzyme on ultraviolet radiation-induced inflammation, immune suppression, and cyclobutane pyrimidine dimer formation in mice.
Exposure of skin to ultraviolet (UV) radiation inhibits the induction of delayed-type hypersensitivity (DTH) responses initiated at a distant, unirradiated site. Recent studies attributed this form of immune suppression to DNA damage in the form of cyclobutane pyrimidine dimers (CPD). In the present study, we investigated the protective defects of sunscreens on UV-induced systemic suppression of DTH to Candida albicans, inflammation, and DNA damage. The photoprotective effects of sunscreen preparations containing 8% octyl-N-dimethyl-p-aminobenzoate, 7.5% 2-ethylhexyl-p-methoxycinnamate, or 6% benzophenone-3 were studied in C3H mice exposed to a single dose of 500 mJ/cm2 UVB radiation from FS40 sunlamps. Inflammation was determined by the amount of skin edema at the site of UV irradiation, and DNA damage was assessed by measuring the frequency of endonuclease-sensitive sites in the epidermis. Application of the sunscreens before UV irradiation gave 75-97% protection against UV-induced edema, 67-91% protection against formation of CPD, but only 30-54% protection against suppression of DTH. In contrast, the topical application of liposomes containing a CPD-specific DNA repair enzyme immediately after UV irradiation resulted in 82% protection against suppression of DTH, but at best, 39% protection against skin edema. These findings demonstrate that sunscreens give less protection against UV-induced immune suppression than against skin edema and CPD formation. Furthermore, they suggest that less DNA damage is required to cause UV-induced immune suppression than to cause sunburn.
Wolf
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P
Department of Immunology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Yarosh
D B
DB
Kripke
M L
ML
D000818:Animals; D011088:DNA Ligases / Q000494:pharmacology*; D043224:Deoxyribonuclease (Pyrimidine Dimer); D003872:Dermatitis / Q000209:etiology*; D004337:Drug Carriers; D004706:Endodeoxyribonucleases / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006968:Hypersensitivity, Delayed / Q000517:prevention & control; D007165:Immunosuppression Therapy; D008081:Liposomes; D051379:Mice; D008809:Mice, Inbred C3H; D011740:Pyrimidine Dimers / Q000096:biosynthesis*; D011833:Radiation Injuries, Experimental; D012867:Skin / Q000378:metabolism; D013473:Sunscreening Agents / Q000494:pharmacology*; D014466:Ultraviolet Rays
D004337:Drug Carriers; D008081:Liposomes; D011740:Pyrimidine Dimers; D013473:Sunscreening Agents; D004706:Endodeoxyribonucleases; D043224:Deoxyribonuclease (Pyrimidine Dimer); D011088:DNA Ligases