Indole-3-carbinol protects against covalent binding of benzo[a]pyrene and N-nitrosodimethylamine metabolites to mouse liver macromolecules

Chem Biol Interact. 1984 Jan;48(1):81-90. doi: 10.1016/0009-2797(84)90008-5.


Benzo[a]pyrene (BaP) and N-nitrosodimethylamine (NDMA) are carcinogens and indirect acting mutagens. A naturally occurring dietary indole, indole-3-carbinol (I-3-C), has been shown to decrease the incidence of aryl hydrocarbon induced neoplasia in experimental animals. We examined the relationship between the ability of I-3-C to alter the rate of carcinogen oxidation and its ability to decrease the rate of covalent binding of carcinogen metabolites to DNA and protein. We found that I-3-C inhibited the covalent binding of NDMA oxidation products to DNA in vitro in proportion to its ability to inhibit carcinogen metabolism. Pretreatment of mice by gavage with I-3-C resulted in no change in the rate of aryl hydrocarbon hydroxylase or NDMA demethylase in hepatic post-mitochondrial supernatant. However, this pretreatment resulted in a 60-90% decrease in the ability of carcinogen oxidative metabolites to bind covalently to DNA or protein in vitro. Similarly, in in vivo experiments, gavage with I-3-C, followed by gavage with BaP or NDMA, resulted in a 63-85% decrease in covalent binding to macromolecules, with no concomitant change in carcinogen metabolism. The results suggest that the in vivo administration of I-3-C may confer protection for hepatic macromolecules against covalent binding of the metabolites of these two indirect acting mutagens.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Aroclors / pharmacology
  • Aryl Hydrocarbon Hydroxylases / metabolism
  • Benzo(a)pyrene
  • Benzoflavones / pharmacology
  • Benzopyrenes / metabolism*
  • Chlorodiphenyl (54% Chlorine)
  • DNA / metabolism
  • Dimethylnitrosamine / metabolism*
  • Indoles / pharmacology*
  • Liver / drug effects
  • Liver / metabolism*
  • Male
  • Methylcholanthrene / pharmacology
  • Mice
  • Mice, Inbred ICR
  • Phenobarbital / pharmacology
  • Rats
  • beta-Naphthoflavone


  • Aroclors
  • Benzoflavones
  • Benzopyrenes
  • Indoles
  • Chlorodiphenyl (54% Chlorine)
  • Benzo(a)pyrene
  • Methylcholanthrene
  • beta-Naphthoflavone
  • DNA
  • indole-3-carbinol
  • Aryl Hydrocarbon Hydroxylases
  • Dimethylnitrosamine
  • Phenobarbital