Interleukin-12-deficient mice are at greater risk of UV radiation-induced skin tumors and malignant transformation of papillomas to carcinomas

Molecular Cancer Therapeutics
Syed M MeeranS K Katiyar

Abstract

Solar UV radiation-induced immunosuppression is a risk factor for nonmelanoma skin cancer. Interleukin (IL)-12 has been shown to possess antitumor activity and inhibit the immunosuppressive effects of UV radiation in mice. In this study, we generated IL-12 knockout (KO) mice on a C3H/HeN background to characterize the role of IL-12 in photocarcinogenesis. After exposure of the mice to UVB (180 mJ/cm2) radiation thrice a week for 35 weeks, the development of UV-induced tumors was more rapid and the tumor multiplicity and tumor size were significantly higher in IL-12 KO mice than their wild-type (WT) counterparts (P < 0.05-0.001). Moreover, the malignant transformation of UVB-induced papillomas to carcinomas was higher in IL-12 KO mice in terms of carcinoma incidence (55%, P < 0.001), carcinoma multiplicity (77%, P < 0.001), and carcinoma size (81%, P < 0.001). As IL-12 has the ability to repair UV-induced DNA damage, we determined this effect in our in vivo IL-12 KO mouse model. We found that UVB-induced DNA damage in the form of cyclobutane pyrimidine dimers was removed or repaired more rapidly in WT mice than IL-12 KO mice. Similarly, the UVB-induced sunburn cell formation is primarily a consequence of DNA damage. It was obser...Continue Reading

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Citations

Nov 10, 2009·Archives of Dermatological Research·Joi A Nichols, Santosh K Katiyar
Nov 26, 2010·Archives of Biochemistry and Biophysics·Santosh K Katiyar
Sep 25, 2008·Nature Reviews. Cancer·Ervin H Epstein
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