Mechanisms of Indole-3-carbinol (13C) anticarcinogenesis: Inhibition of aflatoxin b 1-dna adduction and mutagenesis by 13C acid condensation products

Abstract

Possible inhibitory mechanisms of indole-3-carbinol (I3C) against aflatoxin B 1, (AFB 1), a potent hepatocarcinogen, were examined in rainbow trout. In the Salmonella assay using a trout post-mitochondrial activation system, 13C itself was not an antimutagen against AFB,. 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 (133'), the major derivative of I3C found in trout liver; and 5,6,11,12,17,18-hexahydrocyclonona[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 μm and greater of 133', CT or RXM showed about 80% inhibition compared with the control. Higher concentrations (70μm) of the various I3C oligomers also inhibited (to a maximum of 55%) mutagenesis of synthetic AFB 1-8,9-epoxide added to the Salmonella assay, in the absence of activating enzymes. 133' inhibited total microsome catalysed AFB 1-DNA binding in vitro in an apparently non-competitive manner ( K is = 27.6 ± 9.4 μM, K is = 37.5 ± 32.2 μM). These results suggest that the anticarcinogenic effect of I3C against AFB 1 in rainbow trout, and perhaps other species, is due in part to inhibition of AFB 1 bioactivation enzymes and to scavenging of the activated AFB 1-8,9-epoxide.