The protective effect of amifostine on ultraviolet B-exposed xeroderma pigmentosum mice

BACKGROUND: Amifostine is a pharmaceutical agent that is used clinically to counteract the side-effects of chemotherapy and radiotherapy. It acts as a free radical scavenger that protects against harmful DNA cross-linking. The purpose of this study was to determine the effect of amifostine on the development of skin cancer in xeroderma pigmentosum (XP) mice exposed to ultraviolet B radiation (UVB). METHODS: Twenty-five XP mice were equally divided into five groups. Group 1 (control) received no amifostine and no UVB exposure. Group 2 also received no amifostine, but was exposed to UVB at a dose of 200 mJ/cm(2) every other day. The remaining groups were subjected to the same irradiation, but were given amifostine at a dose of 50 mg/kg (group 3), 100 mg/kg (group 4), or 200 mg/kg (group 5) immediately prior to each exposure. RESULTS: No tumours were seen in the control group. The animals in group 2 (no amifostine) developed squamous cell carcinoma (SCC) at 3.5–4.5 months (mean 3.9 months). Groups 3 and 4 (low- and medium-dose amifostine) developed SCC at 4.0–7.0 months (mean 5.3 months), representing a statistically significant delay in tumour presentation (p = 0.04). An even greater delay was seen in group 5 (high-dose amifostine), which developed SCC at 7.0–9.0 months (mean 8.5 months, p < 0.001 versus groups 3 and 4). Ocular keratitis developed in all animals except the unexposed controls and the high-dose treatment group. CONCLUSION: Treatment with amifostine significantly delays the onset of skin cancer and prevents ocular keratitis in UVB-exposed XP mice.