Protection by indole-3-carbinol against covalent binding of benzo[a]pyrene metabolites to mouse liver DNA and protein.
Indole-3-carbinol (I-3-C) is a compound present in many cruciferous vegetables that has been shown to reduce aryl hydrocarbon-induced neoplasia in experimental animals. We examined the relationship between the ability of I-3-C to alter the activity of hepatic aryl hydrocarbon hydroxylase (AHH), and its ability to inhibit the covalent binding of benzo[a]pyrene (BaP) metabolites to DNA and protein. Using an in vitro system and a hepatic postmitochondrial fraction from mice that had been treated by gavage with I-3-C, we found that up to 90% of the covalent binding of BaP metabolites to macromolecules was eliminated, while AHH activity was unchanged. In experiments in vivo, treatment of mice by gavage with I-3-C before [14C]BaP resulted in up to an 80% decrease in covalent binding of 14C to DNA or protein with no concomitant decrease in hepatic AHH activity. These results suggest that I-3-C administered in vivo confers protection against the binding of BaP oxidation products to hepatic cellular macromolecules.
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000378:metabolism*; D004247:DNA / Q000378:metabolism*; D004790:Enzyme Induction; D007211:Indoles / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D011506:Proteins / Q000378:metabolism*
D001580:Benzopyrenes; D007211:Indoles; D011506:Proteins; D001564:Benzo(a)pyrene; D004247:DNA; C016517:indole-3-carbinol; D001189:Aryl Hydrocarbon Hydroxylases