Chemoprevention of Chemically-Induced Mammary Carcinogenesis by indole-3-carbinol

Anticancer Res. May-Jun 1995;15(3):709-16.

Abstract

Indole-3-carbinol, a component of cruciferous vegetables, was evaluated for it efficacy in the prevention of chemically-induced mammary tumors using three different protocols. Because this compound was unstable, it was administered by gavage rather than in the diet. A preliminary dose range study revealed that dose levels of 100 and 50 mg/day, 5x/week, were not toxic to female Sprague-Dawley rats. Initial studies in the DMBA model showed that administering indole-3-carbinol during the initiation and promotion phases were highly effective chemopreventive methods (91-96% reduction in cancer multiplicity). Subsequent studies showed that the administration of indole-3-carbinol only during the initiation phase (7 days prior to until 7 days post DMBA) was also highly effective as a chemopreventive agent. Determination of enzyme levels in the livers of animals treated long-term with indole-3-carbinol showed high levels of induction of various phase I and phase II drug metabolizing enzymes. Finally, indole-3-carbinol when administered both prior to and after MNU (a direct acting carcinogen) caused a significant decrease (65%) in mammary tumor multiplicity. These results support previous studies that indole-3-carbinol can prevent mammary carcinogenesis by direct and indirect acting carcinogens. Therefore, indole-3-carbinol might be a good candidate for chemoprevention of breast cancer in women.

Publication types

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

MeSH terms

  • 9,10-Dimethyl-1,2-benzanthracene
  • Animals
  • Anticarcinogenic Agents / therapeutic use*
  • Cytochrome P-450 CYP2B1
  • Cytochrome P-450 Enzyme System / biosynthesis
  • Cytochrome P-450 Enzyme System / metabolism
  • Female
  • Gene Expression / drug effects
  • Glutathione Transferase / biosynthesis
  • Indoles / therapeutic use*
  • Male
  • Mammary Neoplasms, Experimental / chemically induced
  • Mammary Neoplasms, Experimental / pathology
  • Mammary Neoplasms, Experimental / prevention & control*
  • Methylnitrosourea
  • Oxidoreductases / biosynthesis
  • Oxidoreductases / metabolism
  • Rats
  • Rats, Inbred F344
  • Rats, Sprague-Dawley
  • Sex Characteristics
  • Substrate Specificity
  • Time Factors

Substances

  • Anticarcinogenic Agents
  • Indoles
  • 9,10-Dimethyl-1,2-benzanthracene
  • Methylnitrosourea
  • Cytochrome P-450 Enzyme System
  • indole-3-carbinol
  • Oxidoreductases
  • Cytochrome P-450 CYP2B1
  • Glutathione Transferase