Growth kinetics and chemoprevention of aberrant crypts in the rat colon

✍ Scribed by Michael J. Wargovich; Charles Harris; Chi-Dai Chen; Cynthia Palmer; Vernon E. Steele; Gary J. Kelloff

• Publisher: John Wiley and Sons
• Year: 1992
• Tongue: English
• Weight: 329 KB
• Volume: 50
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/jcb.240501110

✦ Synopsis

Single and multiple colonic crypts exhibiting dysplasia that are detectable insifu by staining of rat colon with methylene blue are called aberrant crypts (AC) and may serve as an intermediate marker for colon cancer. In a characterization study, we have established the kinetics of AC growth and development over a period of 20 d following injectionof ratswiththecarcinogenazoxymethane (AOM). AC are not present at 5dpost-injection, but are aconstantfeature at 10 d and thereafter. Multiple AC, presumably clonal, begin to evolve at 10 d and are consistent by 20 d, forming incipient microadenomata. We have examined 20 candidate chemopreventive agents for inhibition of AC. All agents were given in AIN-76 diet, at two dose levels, with injections of AOM. AC were measured after 5 weeks of growth. Among the most active AC-inhibiting agents were BHA, DFMO, quercetin, diallyl sulfide, 188-glycyrrhetinic acid, and ascorbyl palmitate. In a postinitiation study, the differentiating agent sodium butyrate was ineffective, but piroxicam was highly effective in modulating AC growth. Further, piroxicam inhibited AC development at all stages of growth from single to polycryptal clusters of AC.

The AC assay shows marked sensitivity and specificity for screening agents for chemoprevention of colon cancer.