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
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antinematodal Agents / pharmacology*
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Arylamine N-Acetyltransferase / genetics
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Arylamine N-Acetyltransferase / metabolism
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Blotting, Western
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Carcinogens / toxicity*
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Carcinoma, Hepatocellular / chemically induced*
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Carcinoma, Hepatocellular / enzymology
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Cytochrome P-450 CYP1A2 / metabolism*
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DNA Primers / chemistry
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Drug Combinations
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Drug Synergism
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Enzyme Induction
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Fenbendazole / pharmacology*
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Glutathione Transferase / metabolism
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Immunoenzyme Techniques
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Liver / drug effects
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Liver / enzymology
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Liver Neoplasms, Experimental / chemically induced*
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Liver Neoplasms, Experimental / enzymology
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Male
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Microsomes, Liver / drug effects
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Microsomes, Liver / enzymology
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Quinoxalines / toxicity*
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Rats
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Rats, Inbred F344
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Reverse Transcriptase Polymerase Chain Reaction
Substances
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Antinematodal Agents
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Carcinogens
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DNA Primers
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Drug Combinations
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Quinoxalines
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Fenbendazole
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2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline
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Cytochrome P-450 CYP1A2
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Arylamine N-Acetyltransferase
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Glutathione Transferase