title: Intake of high-fat diet stimulates the risk of ultraviolet radiation-induced skin tumors and malignant progression of papillomas to carcinoma in SKH-1 hairless mice.
abstract: Previously, we showed that administration of a high-fat diet (HF-diet) to C57BL/6 mice exacerbates their response to short-term UVB radiation-induced inflammation in the skin. To explore the effects of an HF-diet on UVB-induced tumorigenesis, we have used the SKH-1 hairless mouse model in which the mice are exposed to UVB radiation (180mJ/cm(2)) three times a week for 24weeks. The development of UVB-induced skin tumors was rapid and the tumor multiplicity and tumor size were significantly higher (P<0.01-0.005) in the mice fed an HF-diet than the mice fed a control-diet (C-diet). Moreover, the malignant progression of UVB-induced papillomas to carcinomas was higher in HF-diet-fed mice. On analysis of tumors and tumor-uninvolved skin samples from the tumor-bearing mice, we found that administration of an HF-diet significantly enhanced the levels of UVB-induced expression of cyclooxygenase-2 (COX-2), prostaglandin E2 (P<0.01), and PGE2 receptors, and activation of NF-κB in the UVB-exposed skin as well as in tumors. In addition the HF-diet enhanced the expression of proinflammatory cytokines, including tumor necrosis factor-α (P<0.01), interleukin (IL)-1β (P<0.01) and IL-6 (P<0.05) in the UVB-exposed skin as well as in tumors. Western blot analysis revealed that HF-diet enhanced the levels of epidermal cell proliferation, phosphatidylinositol 3-kinase and phosphorylation of Akt at Ser(473) in UVB-exposed skin and skin tumors. Collectively, these data demonstrate that the regular consumption of an HF-diet increases the risk of photocarcinogenesis in mice and that this is associated with enhanced expression of inflammatory mediators in the UVB-exposed skin and tumors.
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Mudit
authors.initials: M
authors.lastname: Vaid
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Tripti
authors.initials: T
authors.lastname: Singh
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Ram
authors.initials: R
authors.lastname: Prasad
authors.affiliation: Department of Dermatology, University of Alabama at Birmingham, Birmingham, AL 35294, USA; Birmingham Veterans Affairs Medical Center, Birmingham, AL 35294, USA. Electronic address: skatiyar@uab.edu.
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Katiyar
mesh_terms: D000818:Animals; D059305:Diet, High-Fat / Q000009:adverse effects*; D018450:Disease Progression; D005260:Female; D051379:Mice; D008812:Mice, Hairless; D009381:Neoplasms, Radiation-Induced / Q000378:metabolism / Q000473:pathology*; D010212:Papilloma / Q000378:metabolism / Q000473:pathology*; D012307:Risk Factors; D012878:Skin Neoplasms / Q000378:metabolism / Q000473:pathology*; D014466:Ultraviolet Rays / Q000009:adverse effects
keywords: C-diet; COX-2; Cyclooxygenase-2; HF-diet; High-fat diet; Malignant progression; PGs; Photocarcinogenesis; Prostaglandins; Skin tumor; UV; control diet; cyclooxygenase-2; high-fat diet; prostaglandins; ultraviolet