| ABSTRACT: |
|
Foci of aberrant crypts are putative preneoplastic lesions of colon
cancer that can be detected in unsectioned colons stained with methylene
blue. The ability of this assay to demonstrate chemopreventive activity
was evaluated. Male Sprague-Dawley rats received two subcutaneous
injections 1 week apart, of 15 mg/kg azoxymethane each. The animals
started to receive the test agents in their diet 1 week prior to the first
injection of azoxymethane and continuously until killed 5 weeks later. The
number of foci of aberrant crypts induced by the treatment of azoxymethane
was reduced from 228 foci/animal without any chemopreventive agent to 151
foci/animal by N-acetylcysteine; to 121 foci/animal by
dehydroepiandrosterone; to 161 by alpha-difluoromethylornithine; and to
121 by 1,2-oxothiazolidine-4-carboxylate. The other agents (diallyl
sulfide, ellagic acid and phenethyl isothiocyanate) did not significantly
alter the number of foci/animal induced by azoxymethane. Animals that did
not receive azoxymethane had an average of 0.72 foci/animal. Our results
suggest that four of the tested agents might reduce azoxymethane-induced
colon cancer, which requires confirmation. Further validation of the foci
of aberrant crypt in the colon assay to screen chemicals for
chemoprevention agents is warranted. |