| ABSTRACT: |
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BACKGROUND & AIMS: Rat colon neoplasms are distributed 60% in the
distal colon (DC) and 40% in the proximal colon (PC), similar to
distribution of colon cancers in the industrialized world. The effects of
chemopreventive agents that affect colon tumor incidence on the
distribution of colon tumors were studied. METHODS: Colon tumor
distribution, numbers, and volumes were measured in the DC and PC of rats
administered azoxymethane (15 mg/kg subcutaneously 2x) as an initiating
agent and fed diets containing various chemopreventive agents. RESULTS: In
control rats, azoxymethane-induced tumor incidence in the DC exceeded that
in the PC, but tumor volume was greater in the PC than the DC. Ellagic
acid showed no chemopreventive effect and maintained the PC-DC colon tumor
gradient. Oltipraz, a modestly effective chemopreventive agent,
principally reduced the incidence of DC tumors.
DL-d-difluoromethylornithine also greatly altered tumor number in the DC
compared with the PC. In contrast, piroxicam (400 ppm) reduced PC tumors
by 82% but DC tumors only by 57%. With all regimens, tumor volume remained
greater in the PC than the DC. CONCLUSIONS: Chemopreventive agents have a
selective regional effect on colon tumorigenesis in the rat. Elucidation
of the mechanism for these differences may help clarify the modes of
action of chemopreventive agents in colon cancer. |