Journal Article

Development of a multi-organ rat model for evaluating chemopreventive agents: efficacy of indole-3-carbinol

Gary Stoner, Bruce Casto, Sherry Ralston, Bill Roebuck, Clifford Pereira and George Bailey

in Carcinogenesis

Volume 23, issue 2, pages 265-272
Published in print February 2002 | ISSN: 0143-3334
Published online February 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.2.265
Development of a multi-organ rat model for evaluating chemopreventive agents: efficacy of indole-3-carbinol

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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.

Keywords: I-3-C, indole-3-carbinol; AFB1, aflatoxin B1; AOM, azoxymethane; ACF, aberrant crypt foci; DMBA, 7,12-dimethylbenz[a]anthracene; DEN, N-nitrosodiethylamine

Journal Article.  6738 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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