Chemoprevention of mouse colon tumors with difluoromethylornithine during and after carcinogen treatment.
alpha-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 CD1 mice (40 per group) received dimethylhydrazine (30 mg/kg/week x 6 weeks, s.c.) and various schedules of DFMO, 1% in drinking water: 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 less than 0.05 A versus B, P less than 0.02 A versus D) and on squamous cell carcinomas of the anus in all groups (P less than 0.001 A versus B, P less than 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.
Tempero
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MA
Omaha Veterans Administration Medical Center, Nebraska 68105.
Nishioka
K
K
Knott
K
K
Zetterman
R K
RK
D000818:Animals; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D004127:Dimethylhydrazines; D000518:Eflornithine / Q000627:therapeutic use*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D011073:Polyamines / Q000097:blood; D012016:Reference Values
D004127:Dimethylhydrazines; D011073:Polyamines; D000518:Eflornithine