Lack of modification of 2-amino-3,8-dimethylimidazo[4,5- f]quinoxaline (MeIQx) rat hepatocarcinogenesis by caffeine, a CYP1A2 inducer, points to complex counteracting influences

2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), one of the most abundant carcinogenic heterocyclic amines in cooked foods, is speculated to be a human liver carcinogen. To test the hypothesis that it is metabolically activated by CYP1A2, we here investigated the effects of caffeine as a CYP1A...

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Bibliographic Details
Published in:Cancer letters 2006-02, Vol.232 (2), p.289-299
Main Authors: Kuribayashi, Masanori, Asamoto, Makoto, Suzuki, Shugo, Hokaiwado, Naomi, Ogawa, Kumiko, Shirai, Tomoyuki
Format: Article
Language:English
Subjects:
Acetyltransferases - genetics
Animals
Bioassays
Caffeine
Caffeine - pharmacology
Carcinogens - toxicity
CDK4
CYP1A2
Cytochrome P-450 CYP1A2 - biosynthesis
Cytochrome P-450 CYP1A2 - genetics
Cytochromes
Enzyme Induction
Kinases
Liver
Liver Neoplasms, Experimental - chemically induced
Male
MeIQx
Membrane Glycoproteins - genetics
NAT2
Oligonucleotide Array Sequence Analysis
p21
Proteoglycans - genetics
Quinoxalines - toxicity
Rats
Rats, Inbred F344
Rodents
Syndecan-2
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Summary:2-Amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), one of the most abundant carcinogenic heterocyclic amines in cooked foods, is speculated to be a human liver carcinogen. To test the hypothesis that it is metabolically activated by CYP1A2, we here investigated the effects of caffeine as a CYP1A2 inducer on MeIQx induced rat hepatocarcinogenesis in a medium-term liver bioassay system. Unexpectedly, no modifying effects of caffeine on MeIQx-induced hepatocarcinogenesis were evident, although up-regulation of CYP1A2 and NAT2 were detected. Therefore, mRNAs extracted from GST-P positive foci and the surrounding liver tissue in each group were analyzed to explore mechanisms in detail. The results suggest that suppression of syndecan-2 (Sdc2) and induction of cell cycle arrest through a p21-dependent pathway might have counter-acted any promotion effects of up-regulation of CYP1A2.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2005.02.041