Prevention by alpha-difluoromethylornithine of skin carcinogenesis and immunosuppression induced by ultraviolet irradiation.
Administration of alpha-difluoromethylornithine (DFMO) to mice was found to inhibit both the cutaneous carcinogenesis and the immunosuppression induced by ultraviolet B (UVB) irradiation. BALB/cAnNTacfBR mice were given 1% F2MeOrn in their drinking water throughout the experiment. After 3 weeks, mice received UVB irradiation consisting of five 30-min exposures per week to banks of six FS40 Westinghouse sunlamps. In the photocarcinogenesis study, mice received a total dose of approximately 1273 kJ m-2. Skin cancer incidence in UV-irradiated mice was 38% 28 weeks after the first UV exposure; DFMO reduced this incidence to 9% (P = 0.025, log-rank test). Although DFMO has been demonstrated to be chemopreventive of chemical carcinogenesis, this is the first report that it is effective against cancers induced by a physical carcinogen. The immunosuppression induced by UVB irradiation prevents the host from rejecting antigenic, syngeneic UV-induced tumors, which normal mice can reject. The level of immunosuppression in UV-irradiated mice treated with DFMO was measured by a passive-transfer assay. Splenocytes from UV-irradiated mice to naive mice prevented the recipients from rejecting 20/24 UV-induced tumor challenges, whereas splenocytes from UV-irradiated mice treated with DFMO did not prevent recipients from rejecting such challenges (2/24 grew). The difference between these values was significant (P less than 0.001, two-sample test for binomial proportions). Phenotypic analysis of splenocytes used in the passive transfer, using a biotin-avidin-immunoperoxidase technique, revealed that DFMO treatment prevented the reduction of Ia expression normally seen in UV-irradiated mice. Thus, administration of DFMO reduced skin carcinogenesis and immunosuppression induced by UVB irradiation.
Gensler
H L
HL
Department of Radiation Oncology, University of Arizona, Tucson 85724.
D000818:Animals; D000518:Eflornithine / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D007165:Immunosuppression Therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D010641:Phenotype; D012867:Skin / Q000276:immunology / Q000528:radiation effects*; D012878:Skin Neoplasms / Q000209:etiology / Q000517:prevention & control*; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000502:physiology; D014466:Ultraviolet Rays
D000518:Eflornithine