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

- Consumption of high-fat diet increases UVB-induced skin tumor development in mice.
- Intake of high-fat diet stimulates progression of UV-induced papilloma to carcinoma.
- Intake of high-fat diet enhances inflammation in UV-exposed skin
- Regular consumption of low-fat diet may inhibit the risk of photocarcinogenesis.

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 (180 mJ/cm2) three times a week for 24 weeks. 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 Ser473 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.