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Natural Killer Cell Activity during UVR-induced Skin Tumor Formation in the Skh Hairless Mouse
Authors:P A Steerenberg  E L Korenromp  H van  Loveren  D Q Mol  L Geerse  F R de  Gruijl
Institution:National Institute of Public Health and the Environment (RIVM), Laboratory for Pathology and Immunobiology, Bilthoven, the Netherlands;Department of Dermatology, Utrecht University, Utrecht, the Netherlands
Abstract:Abstract— We analyzed natural killer (NK) cell activity in the hairless albino Skh/HR1 mouse, to study whether the NK cell activity plays a role during UV radiation (UVR)-induced carcinogenesis. In 4 h 5lCr-release assays, spleen lymphocytes of specific pathogen-free (spf) Skh/HR1 mice displayed 5–10% spontaneous NK cell activity. This was comparable to NK ceil activity in C57BI/6, C3H and athymic NMRI nu/nu mice, which were also kept under spf conditions. In all strains investigated, the low spontaneous NK cell activity could be increased up to 20–30% by intraperitoneal administration of polyinosinic: polycytidylic acid (polyI:C), a standardized in vivo NK cell induction method. The polyI:C potentiation of NK cells in Skh/HR1 mice was similar to that in C57Bl/6 and NMRI, but significantly less than in C3H mice. Chronic daily UV irradiation according to a protocol that was also used for induction of carcinogenesis (11–12 weeks, 95 mJ/cm2 of UV exposure from FS40 sunlamps) did not decrease NK cell activity on a cell for cell basis. Neither was the inducibility of NK spleen cell activity with poly I: C in Skh/HR1 mice during UV exposure reduced. Based on total organ basis, the pooled lymph node cells (axillary, mandibulary and inguinal lymph node) showed a doubling of NK cell activity ( P < 0.001), mainly due to an almost 100% increase in the number of lymph node cells. In conclusion, UVR does not suppress the normal or inducible NK cell activity at the time of clinical appearance of skin tumors. This suggests that such suppression of NK cell activity is not likely to contribute to UVR-induced carcinogenesis in the Skh/HRl strain.
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