UV irradiation augments lymphoid malignancies in mice with one functional copy of wild-type p53

Epidemiological studies have suggested an association between exposure to s olar UV radiation and the incidence of lymphoid malignancies, which has inc reased substantially worldwide during the last two decades. Findings from a nimal studies have raised the question of whether UV radiation might influe nce the development of lymphoid malignancies by means of its immunosuppress ive effect. In this study, we examined the effect of UV irradiation on the development of lymphoid malignancies in mice with no or only one functional copy of p53. Mice that lack both copies of p53 spontaneously develop high frequency of lymphoid malignancies in the thymus and spleen. p53 heterozygo us mice with only one copy of the wild-type allele also develop lymphoid ma lignancies, but with a much lower frequency and a long latent period. In ou r study using mice of the C57BL/6 background, only one of the unirradiated mice lacking one copy of p53 (p53(+/-)) spontaneously developed a lymphoid tumor (6%), whereas 88% of UV-irradiated p53(+/-) mice developed lymphoid t umors in the spleen or liver. None of the control or UV-irradiated p53 wild -type mice developed lymphoid tumors during the 60-week observation period. Both UV-irradiated and unirradiated mice lacking both copies of p53 (p53(- /-)) rapidly developed thymic lymphomas and/or lymphoid tumors in spleen or liver. All of the lymphoid tumors tested were of T cell type. The immune r esponses of the mice to contact sensitization were identical and were suppr essed to the same extent by UV irradiation regardless of the genotype. Thes e results indicate that differences in immune reactivity do not account for the different effects of UV radiation on lymphoid malignancies and, in add ition, that p53 is not required for generation of T cell-mediated immunity. Interestingly, whereas p53 mutations or loss of heterozygosity did not acc ount for the accelerated development of lymphoid tumors in UV-irradiated p5 3(+/-) mice, deletions in the p16(INK4a) gene were quite common. These data provide the experimental evidence that UV irradiation induces lymphoid neo plasms in genetically susceptible mice and support the hypothesis that exte nsive sunlight exposure contributes to the induction of lymphoma in humans.