Lack of modification of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx)-induced hepatocarcinogenesis in rats by fenbendazole--a CYP1A2 inducer.
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.
First Department of Pathology, Nagoya City University Medical School, 1 Kawasumi, Mizuho-cho, Mizuho-ku, 467-8601, Nagoya, Japan. shugo@med.nagoya-u.ac.jp
Shugo
S
Suzuki
Satoru
S
Takahashi
Makoto
M
Asamoto
Shingo
S
Inaguma
Tadashi
T
Ogiso
Masao
M
Hirose
Tomoyuki
T
Shirai
D000818:Animals; D000969:Antinematodal Agents / Q000494:pharmacology*; D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D015153:Blotting, Western; D002273:Carcinogens / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000139:chemically induced* / Q000201:enzymology; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D004338:Drug Combinations; D004357:Drug Synergism; D004790:Enzyme Induction; D005273:Fenbendazole / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000378:metabolism; D007124:Immunoenzyme Techniques; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced* / Q000201:enzymology; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D011810:Quinoxalines / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000969:Antinematodal Agents; D002273:Carcinogens; D017931:DNA Primers; D004338:Drug Combinations; D011810:Quinoxalines; D005273:Fenbendazole; C036990:2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline; D019388:Cytochrome P-450 CYP1A2; D001191:Arylamine N-Acetyltransferase; D005982:Glutathione Transferase