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

Abstract

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.

• Authors: S M Fischer, M Lee, R A Lubet
• Journal: Carcinogenesis (Carcinogenesis) Vol. 22 Issue 1 Pg. 83-8 (Jan 2001) ISSN: 0143-3334 [Print] England
• PMID: 11159745 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Anticarcinogenic Agents
• Antineoplastic Agents
• Ornithine Decarboxylase Inhibitors
• Ornithine Decarboxylase
• Eflornithine

Topics

• Animals
• Anticarcinogenic Agents (pharmacology)
• Antineoplastic Agents (pharmacology)
• Cell Division (drug effects, radiation effects)
• Eflornithine (pharmacology)
• Enzyme Induction (radiation effects)
• Female
• Keratinocytes (cytology, drug effects, radiation effects)
• Mice
• Mice, Hairless
• Neoplasms, Radiation-Induced (drug therapy, etiology, prevention & control)
• Ornithine Decarboxylase (biosynthesis, metabolism)
• Ornithine Decarboxylase Inhibitors
• Skin (drug effects, enzymology, radiation effects)
• Skin Neoplasms (drug therapy, etiology, prevention & control)
• Ultraviolet Rays (adverse effects)