Lack of Modification of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)-induced Hepatocarcinogenesis in Rats by Fenbendazole--A CYP1A2 Inducer

Cancer Lett. 2002 Nov 8;185(1):39-45. doi: 10.1016/s0304-3835(02)00243-4.

Abstract

Fenbendazole (FBZ) is an anthelmintic drug known to be a potent CYP1A2 inducer. Combined effects of FBZ on 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)-induced hepatocarcinogenesis in rats were investigated using a medium-term liver bioassay system. No modifying influence was found in terms of glutathione S-transferase placental-form positive foci development although CYP1A2 protein expression in the livers of rats that were given MeIQx and FBZ was 2.3-fold higher than with MeIQx alone. NAT2 mRNA expression did not differ among the groups as revealed by quantitative reverse transcriptase-polymerase chain reaction analysis. These results suggest that elevated CYP1A2 expression is not sufficient to enhance MeIQx-induced hepatocarcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antinematodal Agents / pharmacology*
  • Arylamine N-Acetyltransferase / genetics
  • Arylamine N-Acetyltransferase / metabolism
  • Blotting, Western
  • Carcinogens / toxicity*
  • Carcinoma, Hepatocellular / chemically induced*
  • Carcinoma, Hepatocellular / enzymology
  • Cytochrome P-450 CYP1A2 / metabolism*
  • DNA Primers / chemistry
  • Drug Combinations
  • Drug Synergism
  • Enzyme Induction
  • Fenbendazole / pharmacology*
  • Glutathione Transferase / metabolism
  • Immunoenzyme Techniques
  • Liver / drug effects
  • Liver / enzymology
  • Liver Neoplasms, Experimental / chemically induced*
  • Liver Neoplasms, Experimental / enzymology
  • Male
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / enzymology
  • Quinoxalines / toxicity*
  • Rats
  • Rats, Inbred F344
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Antinematodal Agents
  • Carcinogens
  • DNA Primers
  • Drug Combinations
  • Quinoxalines
  • Fenbendazole
  • 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline
  • Cytochrome P-450 CYP1A2
  • Arylamine N-Acetyltransferase
  • Glutathione Transferase