Journal Article

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

Susan M. Fischer, Marilyn Lee and Ronald A. Lubet

in Carcinogenesis

Volume 22, issue 1, pages 83-88
Published in print January 2001 | ISSN: 0143-3334
Published online January 2001 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/22.1.83
Difluoromethylornithine is effective as both a preventive and therapeutic agent against the development of UV carcinogenesis in SKH hairless mice

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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.

Keywords: BrdU, 5-bromo-2′-deoxyuridine; DFMO, d,l-α-difluoro-methylornithine; LI, labeling index; ODC, ornithine decarboxylase.

Journal Article.  4436 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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