Inhibition of UVB-induced skin carcinogenesis in SKH-1 mice by green tea, caffeine and running wheel exercise may be related to increased activity and decreased body fat.

摘要

The hypothesis of this dissertation is that treatments that increase locomotor activity will reduce ultraviolet-B light (UVB)-induced skin carcinogenesis in SKH-1 mice. As oral administration of green tea and caffeine to SKH-1 mice has been shown to inhibit UVB-induced skin carcinogenesis, the present studies analyzed the effect of green tea and caffeine for 16 weeks on locomotor activity and body fat. Furthermore, the effect of topical caffeine on locomotor activity was investigated. Green tea and caffeine significantly increased twenty-four hour and dark cycle activity, but decreased light cycle activity. Topical caffeine also significantly increased twenty-four hour activity. While chronic, oral treatment of green tea or caffeine did not cause significant changes in monoamine concentrations, the equivalent daily dose of caffeine consumed by mice significantly increased striatal dopamine concentrations after IP administration. In addition, green tea and caffeine significantly decreased the weight of the parametrial fat pads, decreased the thickness of the dermal fat layer, and increased the thickness of the dermal muscle layer. While the caffeine group consumed significantly more food and caffeine, body weights were not different between groups.; In a second set of studies, animals were allowed to increase activity by voluntary running wheel exercise. Subsequent to 16 week high-risk UVB exposure, animals were divided into running wheel or no wheel groups for 14 weeks. Compared to the no wheel group, the running wheel group had increased tumor latency, tumor incidence, tumor number, and tumor volume. In addition, running wheel animals had significantly decreased parametrial fat pad weight and dermal fat layer thickness, despite consuming more food and water.; In a complete carcinogenesis model, animals were divided into no wheel or running wheel groups for 33 weeks while UVB exposed. The running wheel group had increased tumor latency, tumor incidence, tumor number, and tumor volume, compared to animals without running wheels. In addition, animals with access to running wheels had significantly decreased parametrial fat pad weight and dermal fat layer thickness, despite consuming more food and water. These data suggest that increased activity, whether consequent to chemical stimulation or voluntary exercise, may be associated with decreased skin carcinogenesis.