Ultraviolet radiation-induced suppression of natural killer cell activity is enhanced in xeroderma pigmentosum group A (XPA) model mice

Xeroderma pigmentosum group A gene-deficient mice easily develop skin cance rs by ultraviolet radiation. Natural killer cells play an important part in tumor surveillance. To study whether ultraviolet radiation-induced suppres sion of natural killer cell function is involved in the high incidence of s kin tumors in patients with xeroderma pigmentosum, we analyzed the number a nd activity of natural killer cells in ultraviolet B-irradiated xeroderma p igmentosum A model mice. The number of natural killer cells in peripheral b lood significantly decreased after ultraviolet B-irradiation only in xerode rma pigmentosum A mice, but those in the spleen were not affected. As compa red with the wild-type mice, the xeroderma pigmentosum A mice displayed a h igher level of spontaneous splenic natural killer cell activity (10%-15% Ir s 3%) and inducible natural killer activity (30%-50% vs 20%-25%) after inje ction of polyinosinic:polycytidylic acid. At 24 h after the last irradiatio n of three and five daily consecutive exposures to 500 mJ per cm(2)-ultravi olet B, however, the natural killer activity in xeroderma pigmentosum A mic e decreased to 60 and 30% of the preirradiated level, respectively, but it did not in the wild-type mice. The depression of natural killer activity in xeroderma pigmentosum A mice recovered to a normal level at 10 and 15 d af ter the last irradiation, respectively. The high incidence of skin cancers in xeroderma pigmentosum patients may be mainly due to a defect in the repa ir of ultraviolet-damaged DNA of cutaneous cells, and possibly also due to an intensified ultraviolet-induced immunosuppression. Moreover, the present study suggests that the enhanced ultraviolet-induced impairment of natural killer function could be partially involved in cancer development.