Effect of inhibitors of oxygen radical and nitric oxide formation on UV radiation-induced erythema, immunosuppression and carcinogenesis.
We investigated whether supplementation of a sunscreen containing the UVB absorber 2-ethyl-hexyl-methoxycinnamate (cinnamate) with oxygen radical inhibitors (ORI) would improve protection from sunburn, immunosuppression and carcinogenesis. Mice were exposed to solar-simulated UV radiation (ssUV) containing a mixture of UVB and UVA. In initial studies, the ORI 2,2'-dipyridyl and N(G)-monomethyl-L-arginine acetate (L-NMMA) were shown to prevent UVA-induced suppression of contact sensitivity (CS) in mice. Addition of these inhibitors to the sunscreen did not affect the sun protection factor (SPF), but lowered the level of edema when mice were exposed to ssUV. Combination of both inhibitors with the sunscreen, however, increased the SPF from 5 to 5.5. The immune protection factor (IPF) of the sunscreen was only 1.18, but addition of neither dipyridyl nor L-NMMA singly or in combination measurably improved immune protection. However, the ORI improved the ability of the sunscreen to prevent carcinogenesis. The results indicate that reactive oxygen or nitrogen species produced in response to UV radiation are important for erythema, immunosuppression and carcinogenesis, and addition of inhibitors improves the protective capacity of sunscreens.
Halliday
G M
GM
Department of Dermatology, Melanoma and Skin Cancer Research Institute, University of Sydney at Royal Prince Alfred Hospital, NSW, Australia. garyh@med.usyd.edu.au
Russo
P A
PA
Yuen
K S
KS
Robertson
B O
BO
D015082:2,2'-Dipyridyl / Q000494:pharmacology*; D000818:Animals; D004890:Erythema / Q000517:prevention & control*; D005609:Free Radicals; D007108:Immune Tolerance / Q000187:drug effects / Q000528:radiation effects*; D051379:Mice; D009381:Neoplasms, Radiation-Induced / Q000517:prevention & control*; D009569:Nitric Oxide / Q000096:biosynthesis; D013473:Sunscreening Agents / Q000494:pharmacology*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D019323:omega-N-Methylarginine / Q000494:pharmacology*
D005609:Free Radicals; D013473:Sunscreening Agents; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D015082:2,2'-Dipyridyl