Carcinogenesis, Vol. 22, No. 1, 83-88,
January 2001
© 2001 Oxford University Press
CANCER BIOLOGY |
Difluoromethylornithine is effective as both a preventive and therapeutic agent against the development of UV carcinogenesis in SKH hairless mice
The University of Texas MD Anderson Cancer Center, Science Park-Research Division, PO Box 389, Park Road 1C, Smithville, TX 78957, USA and
1 Division of Cancer Prevention and Control, National Institutes of Health, Bethesda, MD 20852, USA
Targeting specific events associated with tumor development represents a rational approach to chemoprevention as well as therapeutic intervention. In this study the ability of difluoromethylornithine (DFMO) to inhibit UV-induced skin carcinogenesis when administered before or after the appearance of tumors was examined. SKH hairless mice were irradiated 3 times per week with 90 mJ/cm2; this dose was increased by 10% weekly to a maximum of 175 mJ/cm2. Mice supplied 0.4% DFMO in the drinking water continuously throughout 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, yielded 3.6 tumors and 100% incidence at 30 weeks. Starting DFMO at 22 weeks, when an average of 2.5 tumors were present, caused regression of tumors for several weeks, followed by a slight rebound. The final tumor number at 30 weeks was 3.0 (96% incidence). Thus, DFMO has strong chemopreventive efficacy, as well as therapeutic activity, against UV-induced skin tumors. Histological and proliferative markers support this conclusion.
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