Piroxicam-induced regression of azoxymethane-induced aberrant crypt foci and prevention of colon cancer in rats.
Piroxicam has been shown to prevent azoxymethane (AOM)-induced aberrant crypt foci and colon cancer in rats. In this communication we evaluate whether piroxicam can also cause regression of precancerous lesions identified as aberrant crypt foci, thus preventing the occurrence of cancer. Male Fischer-344 rats were administered 0.125 g/kg piroxicam in their diet starting either 1 week prior to or 12 weeks after a single subcutaneous injection of AOM (30 mg/kg body wt). The yield of aberrant crypt foci and of colon adenomas and adenocarcinomas was determined at 5, 12, 27 and 37 weeks after administering the AOM respectively. When piroxicam was administered starting 1 week prior to AOM the yield of aberrant crypt foci at the three initial time points was reduced. When the administration of piroxicam was delayed until 12 weeks after AOM the yield of aberrant crypt foci was reduced from 53.8 +/- 8.1 foci/colon at 12 weeks to 11.1 +/- 2.0 at 27 weeks. At 37 weeks after administering AOM the yield of colon tumors was 0.59 +/- 0.11 tumors/animal, while in rats administered piroxicam beginning either 1 week prior to or 12 weeks after AOM the yield was similarly reduced to 0.14 +/- 0.07 and 0.17 +/- 0.07 tumors/animal respectively. Thus piroxicam was demonstrated not only to prevent, but also to cause regression of aberrant crypt foci, both of which were associated with the prevention of colon tumors.
Pereira
M A
MA
Environmental Health Research and Testing Inc., Lexington, KY 40503, USA.
Barnes
L H
LH
Steele
V E
VE
Kelloff
G V
GV
Lubet
R A
RA
D000230:Adenocarcinoma / Q000139:chemically induced / Q000517:prevention & control; D000236:Adenoma / Q000139:chemically induced / Q000517:prevention & control; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D001397:Azoxymethane; D002273:Carcinogens; D003106:Colon / Q000187:drug effects*; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D004354:Drug Screening Assays, Antitumor; D008297:Male; D010894:Piroxicam / Q000627:therapeutic use*; D011230:Precancerous Conditions / Q000139:chemically induced / Q000517:prevention & control*; D051381:Rats; D011916:Rats, Inbred F344
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002273:Carcinogens; D010894:Piroxicam; D001397:Azoxymethane