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Inhibition of aberrant crypt growth by non‐steroidal anti‐inflammatory agents and differentiation agents in the rat colon
Author(s) -
Wargovich Michael J.,
Chen Chi Dai,
Harris Charles,
Yang Eileen,
Velasco Marco
Publication year - 1995
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.2910600415
Subject(s) - aberrant crypt foci , crypt , colorectal cancer , dysplasia , retinoic acid , aspirin , cancer research , biology , pathology , sulindac , carcinogen , medicine , pharmacology , cancer , biochemistry , colonic disease , nonsteroidal , gene
Aberrant crypts are aggregates of single to multiple colonic crypts evidencing hallmarks of dysplasia and may be the earliest detectable pathological 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 carcinogen. In the other, the objective of this study, aberrant crypts were induced in F344 rats by parenteral injection of the colon carcinogen azoxymeth‐ane (AOM) and allowed to develop for 4 weeks, when an average of 90‐100 aberrant crypt foci per colon were found in the methylene blue‐stained colon. Then, during the second 4 weeks of the experiment, aberrant crypts were allowed to further develop to a frequency of > 150 foci per colon, a time when multi‐crypt foci were observed. During this time we tested the inhibitory effects of 4 analgesic drugs and 2 differentiation agents for effects of aberrant crypt growth and development. We found the non‐steroidal anti‐inflammatory drugs piroxicam, aspirin and ibuprofen, but not acetaminophen, to be effective in suppressing aberrant crypt formation or the progression to foci of multiple aberrant crypts. Treatment with chemo‐suppressing agents 13‐ cis ‐retinoic acid (13‐cRA) and 4‐hydroxy‐phenretinamide (4‐HPR), known differentiating agents, however, did suppress expansion of aberrant crypt foci, with 13‐cRA being the much more potent agent.