Most Effective Colon Cancer Chemopreventive Agents in Rats: A Systematic Review of Aberrant Crypt Foci and Tumor Data, Ranked by Potency

Abstract

Potential chemopreventive agents for colorectal cancer are assessed in rodents. We speculated that the magnitude of the effect is meaningful and ranked all published agents according to their potency. Data were gathered systematically from 137 articles with the aberrant crypt foci (ACF) end point and from 146 articles with the tumor end point. The potency of each agent to reduce the number of ACF is listed in one table and the potency of each agent to reduce the tumor incidence in another table. Both tables are shown in this review and on a website with sorting abilities (http://www.inra.fr/reseau-nacre/sci-memb/corpet/indexan.html). Potency was estimated as the ratio of the value in control rats to the value in treated rats. From each article, only the most potent agent was kept, except in articles reporting the effect of more than seven agents. Among the 186 agents in the ACF table, the median agent reduced the number of ACF by one-half. The most potent agents to reduce azoxymethane-induced ACF were Pluronic, polyethylene glycol, perilla oil with beta-carotene, and sulindac sulfide. Among the 160 agents in the tumor table, the median agent reduced the tumor incidence in rats by one-half. The most potent agents to reduce the incidence of azoxymethane-induced tumors were celecoxib, a protease inhibitor from soy, difluoromethylornithine with piroxicam, polyethylene glycol, and a thiosulfonate. For the 57 agents present in both tables, a significant correlation (r) was found between the potencies against ACF and tumors (r = 0.45, P < 0.001); without celecoxib, a major outlying point in the correlation, r = 0.68 (P < 0.001, n = 56). In conclusion, this review gathers most known chemopreventive agents, ranks the most promising agents against colon carcinogenesis in rats or mice, and further supports the use of ACF as a surrogate end point for tumors in rats.

Meat Processing and Colon Carcinogenesis: Cooked, Nitrite-Treated, and Oxidized High-Heme Cured Meat Promotes Mucin-Depleted Foci in Rats

“…MDF thus seem better predictors of colon carcinogenesis than ACF are. However, we decided to show both MDF and ACF data because ACF have already been used in >1,000 published studies (43). The MDF-promoting [dark cooked meat with nitrite, oxidized] meat was a cooked shoulder of pork supplemented with sodium nitrite and kept unwrapped at 4°C for 5 days: It models a piece of cooked ham that has been kept in a refrigerator.…”

A pilot randomised controlled trial to reduce colorectal cancer risk markers associated with B-vitamin deficiency, insulin resistance and colonic inflammation

“…However, colonic inflammation, as assessed by faecal GMP in rodents, can be reduced by the demulcent, polyethylene glycol (PEG 8000) (Karlsson et al, 2005). This agent also reduces experimental colon carcinogenesis to a remarkable degree (Corpet and Tache, 2002). Although some oligosaccharides are known demulcents, no effort appears to have been made to identify such an effect with the use of faecal GMP, which could provide a simple assay for agents with possible protective effects.…”

Mucin‐depleted foci have β‐catenin gene mutations, altered expression of its protein, and are dose‐ and time‐dependent in the colon of 1,2‐dimethylhydrazine‐treated rats

“…Cellular localization and gene mutations of b-catenin were studied also in colonic tumors after DMH as well as in aberrant crypt foci (ACF) identified in HID-AB stained colon. Moreover, we studied the time-course and dose dependence of MDF and we compared MDF to ACF, which have been extensively characterized in rodents 2,5,6 and humans, 3,4 widely used for predicting carcinogenesis, 13 with a few correlation problems. 14,15 Material and methods Animals and carcinogen treatment F344 male rats aged 4-5 weeks (Nossan, Correzzana, Milan, Italy) were housed according to the European Union Regulations on the Care and Use of Laboratory Animals 16 and fed a high-fat diet (23% corn oil w/w) whose composition is based on the AIN-76 diet.…”