INHIBITION OF ABERRANT CRYPT GROWTH BY NONSTEROIDAL ANTIINFLAMMATORY AGENTS AND DIFFERENTIATION AGENTS IN THE RAT COLON

Aberrant crypts are aggregates of single to multiple colonic crypts ev idencing hallmarks of dysplasia and may be the earliest detectable pat hological lesions for colon cancer. The aberrant crypt assay has been developed in 2 protocols. In one, putative chemoprevention agents are tested for inhibitory effects when administered concomitantly with a c arcinogen. In the other, the objective of this study, aberrant crypts were induced in F344 rats by parenteral injection of the colon carcino gen azoxymethane (AOM) and allowed to develop for 4 weeks, when an ave rage of 90-100 aberrant crypt foci per colon were found in the methyle ne blue-stained colon. Then, during the second 4 weeks of the experime nt, aberrant crypts were allowed to further develop to a frequency of > 150 foci per colon, a time when multi-crypt foci were observed. Duri ng this time we tested the inhibitory effects of 4 analgesic drugs and 2 differentiation agents for effects of aberrant crypt growth and dev elopment. We found the non-steroidal anti-inflammatory drugs piroxicam , aspirin and ibuprofen, but not acetaminophen, to be effective in sup pressing aberrant crypt formation or the progression to foci of multip le aberrant crypts. Treatment with chemo-suppressing agents 13-cis-ret inoic acid (13-cRA) and 4-hydroxy-phenretinamide (4-HPR), known differ entiating agents, however, did suppress expansion of aberrant crypt fo ci, with 13-cRA being the much more potent agent. (C) 1995 Wiley-Liss, Inc.