Abstract
Epidemiological studies support a link between cumulative sun exposure and cutaneous squamous cell carcinoma (SCC) development. However, the presumed effects of extended ultraviolet light B (UVB) exposure on tumorigenesis in the sexes have not been formally investigated. We examined differences in ultimate tumorigenesis at 25 weeks in mice exposed to UVB for either 10 or 25 weeks. Additionally, we investigated the effect of continued UVB exposure on the efficacy of topical treatment with anti-inflammatory (diclofenac) or antioxidant (C E Ferulic or vitamin E) compounds on modulating tumorigenesis. Vehicle-treated mice in the 25-week UVB exposure model exhibited an increased tumor burden and a higher percentage of malignant tumors compared to mice in the 10-week exposure model, which correlated with increases in total and mutant p53-positive epidermal cells. Only topical diclofenac decreased tumor number and burden in both sexes regardless of UVB exposure length. These data support the commonly assumed but not previously demonstrated fact that increased cumulative UVB exposure increases the risk of UVB-induced SCC development and can also affect therapeutic efficacies. Our study suggests that cessation of UVB exposure by at-risk patients may decrease tumor development and that topical NSAIDs such as diclofenac may be chemopreventive.
Highlights
Epidemiological studies where patients self-report the amount of sun they have been exposed to over their lifetime have been the main source of the described link between cumulative, lifetime sunlight exposure and the development of cutaneous squamous cell carcinoma
Male mice treated with vehicle in the 25-week ultraviolet light B (UVB) exposure model developed a 2.7-fold increase in tumor number (P < 0.0001, Figure 1(a)) and a 4.2-fold higher tumor burden (P = 0.0006, Figure 1(b)) compared to vehicle-treated mice in the 10-week UVB exposure model
Female mice in the 25-week model treated with vehicle displayed a 6.75-fold increase in tumor number (P < 0.0001, Figure 1(a)) and a 15.3-fold increase in tumor burden (P < 0.0001, Figure 1(b)) compared to vehicletreated mice in the 10-week UVB exposure model
Summary
Epidemiological studies where patients self-report the amount of sun they have been exposed to over their lifetime have been the main source of the described link between cumulative, lifetime sunlight exposure and the development of cutaneous squamous cell carcinoma. Because the Skh-1 mice are hairless, tumors can be observed and their progression was tracked over time with relatively no discomfort for the mice. After chronic UV exposure, shaved, haired mice can develop fibrosarcomas originating from the dermis [3], whereas the induction of tumors in hairless mice via chronic exposure of non-burn-inducing low UVB levels leads almost exclusively to epidermal squamous cell carcinoma and precursor development [4], which correlates to what is observed in UV-induced skin cancer in humans
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