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

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 observed that UVB-induced sunburn cells were repaired rapidly in WT mice compared with IL-12 KO mice. The rapid removal or repair of UV-induced cyclobutane pyrimidine dimers or sunburn cells will result in reduced risk of photocarcinogenesis. Taken together, our data show that IL-12 deficiency is associated with the greater risk of photocarcinogenesis in mice, and this may be due to reduction in damaged DNA repair ability.

• Authors: Syed M Meeran, Sudheer K Mantena, Sreelatha Meleth, Craig A Elmets, Santosh K Katiyar
• Journal: Molecular cancer therapeutics (Mol Cancer Ther) Vol. 5 Issue 4 Pg. 825-32 (Apr 2006) ISSN: 1535-7163 [Print] United States
• PMID: 16648552 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Interleukin-12

Topics

• Animals
• Carcinoma (diagnostic imaging, genetics, immunology)
• Cell Transformation, Neoplastic
• Interleukin-12 (deficiency, genetics, physiology)
• Mice
• Mice, Knockout
• Papilloma (diagnostic imaging, genetics, immunology)
• Radionuclide Imaging
• Skin Neoplasms (diagnostic imaging, genetics, immunology)
• Ultraviolet Rays