Sunlight-induced nonmelanoma skin cancer is the most revalent cancer in the United States with more than one million cases per year (almost as many cases as for all of the other cancers combined), and the number of these cancers has been increasing in recent years. The reasons for this increase are not known. Although most non-melanoma skin cancers are cured by surgical removal, deaths from these cancers continue to occur. We have developed a novel animal model that resembles sunlight-induced skin cancer in humans who receive heavy exposure to sunlight early in life and who develop skin cancer later in life in the absence of additional heavy sunlight exposure. In this model, SKH-1 mice are treated with low doses of UVB for 20 weeks and UVB irradiation is stopped. These mice have no tumors, but they have a high risk of developing skin tumors over the next several months in the absence of further UVB irradiation (high risk mice), and these mice can be used for evaluating tumorigenic and chemopreventive agents. In a recent study, we found that topical applications of several different commercially available moisturizing creams to UVB-pretreated high-risk mice, in the absence of further UVB irradiation, enhanced the formation of skin tumors (tumor-promoting effect). (See Lu et al in J. Invest. Dermatol. 129: 468-475, 2009.) We hypothesize that these tumorigenic commercial creams increase inflammation, stimulate proliferation, and inhibit apoptosis in the epidermis prior to tumor formation and in tumors of UVB pretreated high-risk mice. We also hypothesize that topical applications of sodium lauryl sulfate, mineral oil and petrolatum (substances present in the tumor-promoting moisturizing creams that we studied and in many other home care products) will be tumorigenic in UVB-pretreated high-risk mice.
Our specific aims are: 1. Analyze the effects of topical applications of tumor-promoting moisturizing creams and their constituents on inflammation, proliferation, and apoptosis in the epidermis of SKH-1 mice pretreated with UVB for 2 weeks (short-term studies). 2. Evaluate the effects of topical applications of tumor-promoting moisturizing creams in UVB pretreated high risk mice on inflammation, proliferation, and apoptosis in the epidermis prior to tumor formation and in tumors and areas of the epidermis away from tumors in tumor-bearing mice (mechanism studies utilizing stored paraffin blocks). 3. Evaluate the tumor-promoting activity of topical applications of sodium lauryl sulfate, mineral oil and petrolatum in UVB-pretreated high-risk mice.
The possibility that commonly used moisturizing creams, cosmetics and other topical home care products contribute to the high and increasing incidence of nonmelanoma skin cancer in the United States (more than one million cases per year) is an important issue requiring careful mechanistic and epidemiology studies. The present proposal attempts to identify tumorigenic components in commonly used moisturizing creams that may increase UVB-induced carcinogenesis and to assess potential mechanisms for the tumorigenic effects of these creams and their constituents. Our study will be helpful for determining biomarkers of risk that can be used for designing epidemiology studies, and we anticipate that our research will also result in the design of safer moisturizing creams, cosmetics and other topically used home care products.
|Bernard, Jamie J; Lou, You-Rong; Peng, Qing-Yun et al. (2014) Inverse relationship between p53 and phospho-Chk1 (Ser317) protein expression in UVB-induced skin tumors in SKH-1 mice. Exp Mol Pathol 96:126-31|
|Bernard, Jamie J; Lou, You-Rong; Peng, Qing-Yun et al. (2014) PDE2 is a novel target for attenuating tumor formation in a mouse model of UVB-induced skin carcinogenesis. PLoS One 9:e109862|
|Lou, Yourong; Peng, Qingyun; Li, Tao et al. (2013) Oral caffeine during voluntary exercise markedly inhibits skin carcinogenesis and decreases inflammatory cytokines in UVB-treated mice. Nutr Cancer 65:1002-13|
|Conney, Allan H; Lou, You-Rong; Nghiem, Paul et al. (2013) Inhibition of UVB-induced nonmelanoma skin cancer: a path from tea to caffeine to exercise to decreased tissue fat. Top Curr Chem 329:61-72|
|Lou, Yourong; Peng, Qingyun; Nolan, Bonnie et al. (2010) Oral administration of caffeine during voluntary exercise markedly decreases tissue fat and stimulates apoptosis and cyclin B1 in UVB-treated skin of hairless p53-knockout mice. Carcinogenesis 31:671-8|
|Heffernan, Timothy P; Kawasumi, Masaoki; Blasina, Alessandra et al. (2009) ATR-Chk1 pathway inhibition promotes apoptosis after UV treatment in primary human keratinocytes: potential basis for the UV protective effects of caffeine. J Invest Dermatol 129:1805-15|
|Lu, Yao-Ping; Lou, You-Rong; Xie, Jian-Guo et al. (2009) Tumorigenic effect of some commonly used moisturizing creams when applied topically to UVB-pretreated high-risk mice. J Invest Dermatol 129:468-75|
|Lu, Yao-Ping; Lou, You-Rong; Peng, Qing-Yun et al. (2008) Effect of caffeine on the ATR/Chk1 pathway in the epidermis of UVB-irradiated mice. Cancer Res 68:2523-9|
|Conney, Allan H; Kramata, Pavel; Lou, You-Rong et al. (2008) Effect of caffeine on UVB-induced carcinogenesis, apoptosis, and the elimination of UVB-induced patches of p53 mutant epidermal cells in SKH-1 mice. Photochem Photobiol 84:330-8|