Anticarcinogenic activity of indole-3-carbinol acid products : ultrasensitive bioassay by trout embryo microinjection

The relative contribution of indole-3-carbinol (I3C) and its acid condensation products to the anticarcinogenic activity of this crucifer phytochemical has been studied using trout embryo microinjection. I3C was treated with 0.07 N HCl to give a reaction mixture (RXM) comprising < 0.5% parent com...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1994-07, Vol.54 (13), p.3617-3619
Main Authors: DASHWOOD, R. H, FONG, A. T, ARBOGAST, D. N, BJELDANES, L. F, HENDRICKS, J. D, BAILEY, G. S
Format: Article
Language:English
Subjects:
Aflatoxin B1 - metabolism
Animals
Anticarcinogenic Agents - administration & dosage
Anticarcinogenic Agents - pharmacology
Biological and medical sciences
Carcinogenesis, carcinogens and anticarcinogens
Chemical agents
DNA - metabolism
Drug Screening Assays, Antitumor
Embryo, Nonmammalian
Indoles - administration & dosage
Indoles - pharmacology
Liver Neoplasms, Experimental - chemically induced
Medical sciences
Microinjections
Oncorhynchus mykiss - embryology
Tumors
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Summary:The relative contribution of indole-3-carbinol (I3C) and its acid condensation products to the anticarcinogenic activity of this crucifer phytochemical has been studied using trout embryo microinjection. I3C was treated with 0.07 N HCl to give a reaction mixture (RXM) comprising < 0.5% parent compound and over 20 products, the most prevalent being the dimer 3,3'-diindolylmethane (I33') and a related cyclic trimer (CT). RXM, I33' or CT was injected into embryos with [3H]aflatoxin B1 (AFB1) and total embryonic DNA was isolated 1, 3, or 10 days postinjection. Compared with controls given AFB1 alone, I3C failed to inhibit carcinogen-DNA binding at any time point. In contrast I33', CT, and RXM inhibited AFB1-DNA binding by an average of 37, 51, and 65%, respectively. Coinjection of AFB1 and 350 microM I3C, RXM, or I33' into trout embryos reduced AFB1-induced hepatocarcinogenesis after 1 year from 43.4% in positive controls to 36.0, 12.2 (P < 0.05), and 24.6% (P < 0.05), respectively. No tumor data were obtained in the AFB1 plus CT group due to poor survival of the embryos posthatching. These results indicate that acid condensation products, not the parent compound, represent the anticarcinogenic species in trout and that their formation in the stomach is a likely prerequisite for I3C anticarcinogenesis.
ISSN:0008-5472
1538-7445