Abstract

Abstract Our previous studies reported that oral administration of caffeine or voluntary exercise may have decreased skin tumor multiplicity, in part, by decreasing fat levels in the dermis and the size of parametrial fat pads. Our studies also showed that surgical removal of the parametrial fat pads (partial lipectomy) enhanced UVB-induced apoptosis in the epidermis. These data suggest that tissue fat may play an important role in regulating UVB-induced apoptosis and skin carcinogenesis. Accordingly, in the present study, we explored the effects of two different types of high fat diets (as described by Rao et al., Cancer Research 61:1927-33, 2001) on UVB-induced complete skin carcinogenesis in SKH-1 hairless mice. Eighty female SKH-1 mice (7-8 weeks old) were equally divided into two groups (40 mice per group). They were irradiated with 30 mJ/cm2 of ultraviolet light B (UVB) once each day, two times per week for 39 weeks. From the beginning of UVB treatment, one group of the mice was given high fat diet containing 32% of polyunsaturated omega-3 fatty acids (HFFO) and the other group of the mice was given high fat diet containing 28% of polyunsaturated omega-6 fatty acids (HFML). Our results showed that although both groups of animals gained weight dramatically, there were no statistical differences on body weight, weight of parametrial fat pad, or thickness of the dermal fat layer. Gross examination showed that HFFO treatment delayed the appearance of UVB-induced skin lesions, decreased the number of mice with tumors and decreased the number and size of tumors per mouse. Histopathological characterization of the skin lesions revealed that HFFO administration decreased the number of squamous cell papillomas per mouse by 64%, decreased the number of keratoacanthomas per mouse by 52% and decreased the number of squamous cell carcinomas per mouse by 46%. In addition to reducing the number of skin tumors, HFFO diet substantially decreased the size of the tumors. That is, the HFFO diet decreased the total volume of squamous cell papillomas per mouse by 98%, decreased the total volume of keratoacanthomas per mouse by 80% and deceased the total volume of squamous cell carcinomas per mouse by 83%. Finally, animals fed the HFFO diet had 22% lower blood levels of tryglycerides (79.3±5.1 mg/dL) than the mice fed the HFML diet (102.0±6.3 mg/dL) (p<0.01), but there was no difference in levels of blood glucose. The effects described here indicate that omega-3 fatty acids in HFFO diet may have beneficial effects against UVB-induced skin carcinogenesis. (Supported by NIH Grant RO1 CA128997) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 968.

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