Regional chemoprevention of carcinogen-induced tumors in rat colon.
OBJECTIVE
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.
Liu
T
T
Gastrointestinal Division, St. Luke's-Roosevelt Hospital Center, College of Physicians and Surgeons, Columbia University, New York, USA.
Mokuolu
A O
AO
Rao
C V
CV
Reddy
B S
BS
Holt
P R
PR
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001397:Azoxymethane; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D000518:Eflornithine / Q000627:therapeutic use; D004610:Ellagic Acid / Q000627:therapeutic use; D008297:Male; D010894:Piroxicam / Q000627:therapeutic use; D011719:Pyrazines / Q000627:therapeutic use; D051381:Rats; D011916:Rats, Inbred F344; D013871:Thiones; D013876:Thiophenes
D016588:Anticarcinogenic Agents; D011719:Pyrazines; D013871:Thiones; D013876:Thiophenes; D010894:Piroxicam; D004610:Ellagic Acid; C026209:oltipraz; D001397:Azoxymethane; D000518:Eflornithine