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8530

Effect of Amifostine on UVB Radiation Induced Skin Tumors in Xeroderma Pigmentosum Mice

Faeza Kazmier, MD, Matthew J. Concannon, MD, and C. Lin Puckett, MD.

Skin cancer is the most common human malignancy in the U.S. and constitutes 50% of all cancers diagnosed every year. There is a positive correlation between skin malignancies and exposure to ultraviolet radiation, specifically UVB light. Patients with Xeroderma pigmentosum (XP) are particularly susceptible to UV-induced damage and are 1000 times more likely to the develop skin cancer by age 20. The only known prevention for development of skin cancer is sun avoidance. Sunscreens reduce the exposure to UV light but do not prevent UV mediated damage. Amifostine (Ethyol, WR-2721, Medimmune, Inc, Gaithersburg, MD) is the first broad-spectrum cytoprotectant approved for clinical use and has been shown to have protective effects from chemotherapy and ionizing radiation therapy by acting as a free radial scavenger. Based on previous studies, when exposed to UVB, 100% of Xeroderma pigmentosum mice developed skin cancer. The purpose of the study is to evaluate the effect of Amifostine on the development of skin cancer in the presence of ultraviolet-B (UVB) radiation.

METHODS: Twenty-five Xeroderma pigmentosum mice were studied over 9 months. Five mice received no UVB exposure or medication (control Group 1). Twenty mice were exposed to 200 mJ/cm2 UVB light every other day. They were separated into 4 equal groups - group# 2: saline intraperitoneal (IP); group# 3: 50 mg/kg amifostine IP; group# 4: 100 mg/kg amifostine IP; and group# 5: 200 mg/kg amifostine IP. The mice were inspected daily and suspicious lesions were biopsied and examined histologically.

RESULTS: In group 1, all mice survived with no tumors. In group 2, initial squamous cell carcinoma (SCC) was seen at 3.5 months and all mice had tumors by 4.5 months. In group 3, the first tumor was at 4 months and all mice developed SCC by 7.5 months. In group 4, the first tumor was at 4 months and all mice developed SCC by 6.5 months. In group 5, first tumor was at 7.5 months and all mice had SCC by 9 months. Two mice (from groups 1 and 2) died from splenic and hepatic injections. There was a significantly lower incidence of SCC in the treated mice (200 mg/kg) compared to the saline and 100 mg/kg groups (p=0.04). The administration of amifostine resulted in a statistically significant delay of onset of first tumor in comparison of all 5 groups (p<0.001) with the most significant results in the higher dosage group.

CONCLUSION: Amifostine results in a statistically significant delay in the development of skin cancer in Xeroderma pigmentosum mice exposed to high levels of UVB radiation.


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