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 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/cm(2); this dose was increased by 10% weekly to a maximum of 175 mJ/cm(2). 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.
Fischer
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The University of Texas MD Anderson Cancer Center, Science Park-Research Division, PO Box 389, Park Road 1C, Smithville, TX 78957, USA. sa83161@odin.mdacc.tmc.edu
Lee
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Lubet
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D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D000518:Eflornithine / Q000494:pharmacology*; D004790:Enzyme Induction / Q000528:radiation effects; D005260:Female; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D051379:Mice; D008812:Mice, Hairless; D009381:Neoplasms, Radiation-Induced / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D009955:Ornithine Decarboxylase / Q000096:biosynthesis / Q000378:metabolism; D065108:Ornithine Decarboxylase Inhibitors; D012867:Skin / Q000187:drug effects / Q000201:enzymology / Q000528:radiation effects; D012878:Skin Neoplasms / Q000188:drug therapy / Q000209:etiology / Q000517:prevention & control*; D014466:Ultraviolet Rays / Q000009:adverse effects
D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D065108:Ornithine Decarboxylase Inhibitors; D009955:Ornithine Decarboxylase; D000518:Eflornithine