TY - JOUR
T1 - Chemoprevention of Mouse Colon Tumors with Difluoromethylornithine during and after Carcinogen Treatment
AU - Tempero, Margaret A.
AU - Knott, Kristen
AU - Zetterman, Rowan K.
AU - Nishioka, Kenji
PY - 1989/11/1
Y1 - 1989/11/1
N2 - 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.
AB - 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.
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M3 - Article
C2 - 2507137
AN - SCOPUS:0024430216
VL - 49
SP - 5793
EP - 5797
JO - Cancer Research
JF - Cancer Research
SN - 0008-5472
IS - 21
ER -