Development of a multi-organ rat model for evaluating chemopreventive agents: efficacy of indole-3-carbinol.
Indole-3-carbinol (I-3-C) is among the most widely and popularly known antiestrogens. Due to its putative chemopreventive action, I-3-C is being marketed to the general public in health food establishments. Although it has been demonstrated to prevent cancer in animal bioassays, I-3-C also acts as a promoter in the liver and colon. Because of this potential dual biological activity, it is important to investigate both the inhibitory and promotional activities of I-3-C in multi-organ tumorigenesis animal models. 7,12-Dimethylbenz[a]anthracene, aflatoxin B1 and azoxymethane were used to initiate mammary, liver and colon carcinogenesis, respectively in female Sprague-Dawley rats. The rats were fed continuously on a diet containing I-3-C for 25 weeks after initiation. I-3-C treatment was begun one week after the last carcinogen treatment had been administered. I-3-C treatment resulted in a delay in latency of mammary tumor formation, but did not alter tumor incidence or multiplicity among survivors. In the colon, the protocol produced a 40% decrease in aberrant colon crypt foci. However, in the liver, it strongly-induced GST-P foci in carcinogen-treated (a four-fold increase in volume percent foci) and in the vehicle controls (a 69-fold increase). These data support previous findings in other rodent and fish tumor models that I-3-C both inhibits and promotes carcinogenesis. The results of this study clearly demonstrate that I-3-C is not an appropriate chemoprotective agent for human use, in spite of its effects in the breast and colon in this rat animal model.
Stoner
Gary
G
Division of Environmental Health Sciences, School of Public Health, College of Medicine and Public Health, The Ohio State University, Columbus, OH, USA. stoner.21@osu.edu
Casto
Bruce
B
Ralston
Sherry
S
Roebuck
Bill
B
Pereira
Clifford
C
Bailey
George
G
D015127:9,10-Dimethyl-1,2-benzanthracene; D016604:Aflatoxin B1; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001397:Azoxymethane; D001835:Body Weight; D002273:Carcinogens; D003110:Colonic Neoplasms / Q000139:chemically induced; D004195:Disease Models, Animal; D005260:Female; D007211:Indoles / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects; D008113:Liver Neoplasms / Q000139:chemically induced; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced; D009153:Mutagens; D009369:Neoplasms / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D016588:Anticarcinogenic Agents; D002273:Carcinogens; D007211:Indoles; D009153:Mutagens; D015127:9,10-Dimethyl-1,2-benzanthracene; D016604:Aflatoxin B1; C016517:indole-3-carbinol; D001397:Azoxymethane