Difluoromethylornithine is effective as both a preventive and therapeutic agent against the development of UV carcinogenesis in SKH hairless mice

Targeting specific events associated with tumor development represents a ra tional approach to chemoprevention as well as therapeutic intervention. In this study the ability of difluoromethylornithine (DFMO) to inhibit UV-indu ced skin carcinogenesis when administered before or after the appearance of tumors was examined. SKH hairless mice were irradiated 3 times per week wi th 90 mJ/cm(2); this dose was increased by 10% weekly to a maximum of 175 m J/cm(2). Mice supplied 0.4% DFMO in the drinking water continuously through out the experiment had an average of 2.0 tumors/mouse (72% incidence) at 30 weeks while controls had an average of 8.2 tumors/mouse (100% incidence). DFMO started after 12 weeks of UV, a time prior to tumor appearance, yielde d 3.6 tumors and 100% incidence at 30 weeks. Starting DFMO at 22 weeks, whe n an average of 2.5 tumors were present, caused regression of tumors for se veral weeks, followed by a slight rebound. The final tumor number at 30 wee ks was 3.0 (96% incidence). Thus, DFMO has strong chemopreventive efficacy, as well as therapeutic activity, against UV-induced skin tumors. Histologi cal and proliferative markers support this conclusion.