Chemoprevention of 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine-induced mammary carcinogenesis in rats

Cancer Lett. 1999 Sep 1;143(2):195-8. doi: 10.1016/s0304-3835(99)00124-x.

Abstract

Modifying effects of dietary exposure of diallyl disulfide (DAD), aspirin, DL-alpha-difluoromethylomithine (DFMO), beta-naphthoflavone (beta-NF), alpha-naphthoflavone (alpha-NF), indole-3-carbinol (I3C) and protocatechuic acid (PCA) on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced mammary carcinogenesis were examined in two experiments with female rats. For both experiments, PhIP in corn oil at a concentration of 85 mg/kg was given to animals via an intragastric tube for eight doses for an initial 4 weeks, and test chemicals were given in the diet (Experiment 1: DAD, 200 ppm; aspirin, 400 ppm; DFMO, 400 ppm; beta-NF, 1000 ppm; Experiment 2: alpha-NF, 1000 ppm; I3C, 1000 ppm; PCA, 2000 ppm) for an initial 4 weeks. The experiments were terminated after 25 weeks. In Experiment 1, exposure of beta-NF decreased the incidence and multiplicity of total mammary tumors (fibroadenoma, intraductal carcinoma and invasive ductal carcinoma) (P < 0.001 and P < 0.0001), and lowered the incidence of ductal carcinoma (P < 0.0001). DAD lowered the incidence of ductal carcinoma and decreased the multiplicity of the total tumors (P < 0.01 and P < 0.005). Furthermore, aspirin decreased the total tumors (P < 0.05). In Experiment 2, alpha-NF decreased the multiplicity of ductal carcinoma (P < 0.05). These results suggest that alpha-NF, beta-NF, DAD or aspirin could be chemopreventing agents for mammary neoplasia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allyl Compounds / pharmacology
  • Allyl Compounds / therapeutic use
  • Animals
  • Anticarcinogenic Agents / pharmacology*
  • Anticarcinogenic Agents / therapeutic use
  • Aspirin / pharmacology
  • Aspirin / therapeutic use
  • Benzoflavones / pharmacology
  • Benzoflavones / therapeutic use
  • Carcinogens / administration & dosage
  • Carcinogens / toxicity*
  • Disulfides / pharmacology
  • Disulfides / therapeutic use
  • Drug Antagonism
  • Eflornithine / pharmacology
  • Eflornithine / therapeutic use
  • Female
  • Hydroxybenzoates / pharmacology
  • Hydroxybenzoates / therapeutic use
  • Imidazoles / administration & dosage
  • Imidazoles / toxicity*
  • Indoles / pharmacology
  • Indoles / therapeutic use
  • Mammary Neoplasms, Experimental / chemically induced*
  • Mammary Neoplasms, Experimental / prevention & control*
  • Rats
  • Rats, Sprague-Dawley
  • beta-Naphthoflavone / pharmacology
  • beta-Naphthoflavone / therapeutic use

Substances

  • Allyl Compounds
  • Anticarcinogenic Agents
  • Benzoflavones
  • Carcinogens
  • Disulfides
  • Hydroxybenzoates
  • Imidazoles
  • Indoles
  • protocatechuic acid
  • diallyl disulfide
  • alpha-naphthoflavone
  • beta-Naphthoflavone
  • 2-amino-1-methyl-6-phenylimidazo(4,5-b)pyridine
  • indole-3-carbinol
  • Aspirin
  • Eflornithine