Mechanisms of indole-3-carbinol (I3C) anticarcinogenesis: inhibition of aflatoxin B1-DNA adduction and mutagenesis by I3C acid condensation products.
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Possible inhibitory mechanisms of indole-3-carbinol (I3C) against aflatoxin B1 (AFB1), a potent hepatocarcinogen, were examined in rainbow trout. In the Salmonella assay using a trout post-mitochondrial activation system, I3C itself was not an antimutagen against AFB1. The study also evaluated: the antimutagenic ability of I3C oligomers; an acid reaction mixture (RXM) of I3C, generated at low pH to simulate I3C products formed under acidic conditions of the stomach; 3,3-diindolylmethane (I33'), the major derivative of I3C found in trout liver; and 5,6,11,12,17,18- hexahydrocyclononal [1,2-b:4,5-b':7,8-b"]triindole , the cyclic trimer of I3C (CT), a derivative of I3C in liver and one of the major components of RXM. Concentrations of 3.5 microM and greater of I33', CT or RXM showed about 80% inhibition compared with the control. Higher concentrations (70 microM) of the various I3C oligomers also inhibited (to a maximum of 55%) mutagenesis of synthetic AFB1-8,9-epoxide added to the Salmonella assay, in the absence of activating enzymes. I33' inhibited total microsome catalysed AFB1-DNA binding in vitro in an apparently non-competitive manner (Kis = 27.6 +/- 9.4 microM, Kii = 37.5 +/- 32.2 microM). These results suggest that the anticarcinogenic effect of I3C against AFB1 in rainbow trout, and perhaps other species, is due in part to inhibition of AFB1 bioactivation enzymes and to scavenging of the activated AFB1-8,9-epoxide.
author list (cited authors)
Takahashi, N., Dashwood, R. H., Bjeldanes, L. F., Williams, D. E., & Bailey, G. S.
complete list of authors
Takahashi, N||Dashwood, RH||Bjeldanes, LF||Williams, DE||Bailey, GS