Development of a multi-organ rat model for evaluating chemopreventive agents: efficacy of indole-3-carbinol. Carcinogenesis 2002 Feb;23(2):265-72
Date
03/02/2002Pubmed ID
11872631DOI
10.1093/carcin/23.2.265Scopus ID
2-s2.0-0036119630 (requires institutional sign-in at Scopus site) 75 CitationsAbstract
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.
Author List
Stoner G, Casto B, Ralston S, Roebuck B, Pereira C, Bailey GMESH terms used to index this publication - Major topics in bold
9,10-Dimethyl-1,2-benzanthraceneAflatoxin B1
Animals
Anticarcinogenic Agents
Azoxymethane
Body Weight
Carcinogens
Colonic Neoplasms
Disease Models, Animal
Female
Indoles
Liver
Liver Neoplasms
Mammary Neoplasms, Experimental
Mutagens
Neoplasms
Rats
Rats, Sprague-Dawley
Time Factors