Chemoprevention of Mouse Colon Tumors with Difluoromethylornithine during and after Carcinogen Treatment

Margaret A. Tempero, Kristen Knott, Rowan K. Zetterman, Kenji Nishioka

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

α-Difluoromethylornithine (DFMO) treatment has been shown to modify carcinogenesis in many experimental tumor models, including skin, breast, and colon. This study was designed to determine whether DFMO treatment can inhibit experimental mouse colon tumors after carcinogen treatment and whether an associated effect of DFMO on cell proliferation in colon mucosa occurs. Male CDi mice (40 per group) received dimethylhydrazine (30 mg/kg/week × 6 weeks, s.c.) and various schedules of DFMO, 1% in drinking waten Group A, none; Group B, following dimethylhydrazine treatment; Group C., during dimethylhydrazine treatment; and Group D, continuously throughout the study. Measurements of RBC polyamine levels showed that DFMO treatment ablated putrescine levels and confirmed that a systemic biological effect was achieved. Analysis of tumor data showed a significant inhibitory effect of DFMO treatment on colon tumor (adenomas and adenocarcinomas) incidence in Groups B (24%) and D (20%) compared to control Group A (52%, P < 0.05 A versus B, P < 0.02 A versus D) and on squamous cell carcinomas of the anus in all groups (P < 0.001 A versus B, P < 0.05 A versus C., A versus D). No consistent effect of DFMO treatment on cell proliferation in colon mucosa was identified. This study supports the hypothesis that DFMO treatment alters events in the postinitiation phases of mouse colon tumorigenesis.

Original languageEnglish (US)
Pages (from-to)5793-5797
Number of pages5
JournalCancer Research
Volume49
Issue number21
StatePublished - Nov 1 1989

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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