This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Maeda, A. Articles by Schwarz, A. Search for Related Content PubMed PubMed Citation Articles by Maeda, A. Articles by Schwarz, A.

Enhanced Photocarcinogenesis in Interleukin-12–Deficient Mice

Departments of ¹ Dermatology and ² Pathology, University Kiel, Kiel, Germany and ³ Department of Dermatology, University Münster, Münster, Germany

Requests for reprints: Thomas Schwarz, Department of Dermatology, University of Kiel, Schittenhelmstrasse 7, D-24105 Kiel, Germany. Phone: 49-431-5971500; Fax: 49-431-5971503; E-mail: tschwarz{at}dermatology.uni-kiel.de.

UV-induced DNA damage is the basis for the development of UV-mediated skin cancer because reduction of DNA damage lowers the risk for photocarcinogenesis. The cytokine interleukin (IL)-12 was shown to exhibit the capacity to reduce UV-induced DNA damage presumably via induction of nucleotide excision repair. Because IL-12 is also produced in the skin, we wondered whether endogenous IL-12 protects from photocarcinogenesis. Therefore, we used knockout mice that lack the IL-12p40 chain and thus do not secrete biologically active IL-12. IL-12p40 knockout (IL-12p40–/–) and wild-type (wt) mice were exposed thrice weekly to UV. Skin biopsies obtained after 6 weeks revealed significantly increased numbers of sunburn cells in IL-12p40–/– mice. Additionally, a higher load of UV-induced pyrimidine dimers could be detected in the skin of UV-exposed IL-12p40–/– mice. Staining of epidermal sheets with an antibody against the tumor suppressor gene p53 revealed a higher number of p53 patches in the skin of IL-12p40–/– mice. After 200 days, first skin tumors developed. Kaplan-Meier analysis indicated a significantly increased probability of tumor development in the IL-12p40–/– mice. In addition, the number of tumors developing in the individual mice was significantly higher in IL-12p40–/– mice than in wt mice. Tumors obtained in IL-12p40–/– mice grew faster than those obtained from wt mice on inoculation into nu/nu mice. This was confirmed in an electrophysiologic assay evaluating the intrinsic invasive potency of tumor cells. Together, these data indicate that IL-12 deficiency is associated with an increased risk to develop UV-induced skin cancer, implying that endogenous IL-12 may protect from photocarcinogenesis. (Cancer Res 2006; 66(6): 2962-9)

This article has been cited by other articles:

				N. Yusuf, T. H. Nasti, J. A. Long, M. Naseemuddin, A. P. Lucas, H. Xu, and C. A. Elmets Protective Role of Toll-like Receptor 4 during the Initiation Stage of Cutaneous Chemical Carcinogenesis Cancer Res., January 15, 2008; 68(2): 615 - 622. [Abstract] [Full Text] [PDF]