REGIONAL CHEMOPREVENTION OF CARCINOGEN-INDUCED TUMORS IN RAT COLON

Background & Aims: Rat colon neoplasms are distributed 60% in the dist al colon (DC) and 40% in the proximal colon (PC), similar to distribut ion of colon cancers in the industrialized world. The effects of chemo preventive agents that affect colon tumor incidence on the distributio n of colon tumors were studied. Methods: Colon tumor distribution, num bers, and volumes were measured in the DC and PC of rats administered azoxymethane (15 mg/kg subcutaneously 2x) as an initiating agent and f ed diets containing various chemopreventive agents. Results: In contro l vats, azoxymethane-induced tumor incidence in the DC exceeded that i n 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 t umor gradient. Oltipraz, a modestly effective chemopreventive agent, p rincipally reduced the incidence of DC tumors. DL-d-difluoromethylorni thine also greatly altered tumor number in the DC compared with the PC . In contrast, piroxicam (400 ppm) reduced PC tumors by 82% but DC tum ors only by 57%. With all regimens, tumor volume remained greater in t he PC than the DC. Conclusions: Chemopreventive agents have a selectiv e regional effect on colon tumorigenesis in the rat. Elucidation of th e mechanism for these differences may help clarify the modes of action of chemopreventive agents in colon cancer.