GENETIC-VARIATION IN LOW-DOSE UV-INDUCED SUPPRESSION OF CONTACT HYPERSENSITIVITY AND IN THE SKIN PHOTOCARCINOGENESIS RESPONSE

Two of the major cutaneous consequences of ultraviolet (UV) radiation exposure are immunosuppression and the development of skin cancer. Thi s study examined whether these effects are genetically determined, Sup pression of contact hypersensitivity by local, low-dose UV radiation w as examined in what have been termed ''UV-susceptible'') and ''UV-resi stant'' strains of mice, C3H/HeJ mice (''UV resistant'') were resistan t to the adverse effects of low-dose UV radiation when normal doses of hapten were applied to W-irradiated skin; however, they were sensitiv e when the amount of hapten used for sensitization was reduced. A simi lar effect was observed in BALB/c cilice ((''UV resistant'') and when the hapten was dimethyl-benz(a)anthracene, thus indicating that the ge netic variation was not strain or hapten specific. Despite the fact th at some strains were sensitive and some were resistant to low-dose UV radiation when high doses of hapten were employed, all strains initial ly sensitized to hapten through W-irradiated skin were found to be unr esponsive when rechallenged on normal skin, no matter what the initial sensitizing dose of hapten was, To determine whether other biologic e ffects of UV also exhibited genetic variation, C3H/HeN and C3H/HeJ mic e were compared for susceptibility to UVB-induced skin cancer formatio n, C3H/HeJ mice developed significantly more tumors than C3H/HeN mice when subjected to a single dose of UV radiation followed by repeated e xposure to the tumor promoter 12-O-tetradecanoyl-phorbol-13-acetate., These studies provide strong evidence that genetic factors influence i ndividual susceptibility to the biologic effects of UV radiation.