Expression of G1 cell cycle regulators in XXXX liver upon repeated exposure to @entity7008 .

@entity7008 @entity49621 @entity7504 @entity11754 @entity409 @entity9533 @entity12003 @entity19087 @entity35
BACKGROUND AND AIMS: Eukaryotic cell cycle is regulated by signal transduction pathways mediated by complexes of cyclin dependent kinases (CDKs) and their partner cyclins, or by interaction with CDK inhibitors. @entity7008 (TA) is a weak hepatocarcinogen causing several types of @entity409 in a dose dependent manner and ultimately producing malignant transformation. We investigated alterations of expression of cell cycle regulators in the @entity35 liver, involved in G1 entry and progression during TA administration. METHODS: We studied expression patterns of @entity12003 , @entity19087 , @entity49621 , @entity7504 ( @entity9533 ) and @entity11754 ( @entity11754 ) during daily intraperitoneal injection of low dose TA (50 mg/kg) till 7 day. We used western blot and immunohistochemistry for detection. RESULTS: Expression of @entity12003 , @entity19087 , @entity49621 and @entity7504 ( @entity9533 ) increased from 6 hour and peaked at 2, 3 day, then decreased next 2 days, and re-increased at 6 day. Cytoplasmo-nuclear translocation of @entity12003 and @entity7504 ( @entity9533 ) was evident within 1 day and prominent at 2 and 7 day. Expression of @entity11754 ( @entity11754 ) increased immediately after TA treatment and remarkably increased from 3 day and progressed till 7 day, showing cytoplasmic location, suggestive of inactive form. Most of in situ immunoreactions occurred at the centrilobular hepatocytes. Concomitant nuclear translocation of @entity7504 ( @entity9533 ) and @entity12003 , different with @entity11754 ( @entity11754 ) suggests that @entity7504 ( @entity9533 ) might be a transporter for nuclear translocation rather than cell cycle inhibitor. CONCLUSIONS: Daily administration of low dose TA makes cell cycle open and G1 progress, possibly due to @entity12003 , @entity19087 and @entity49621 , their transporter @entity7504 ( @entity9533 ), and inactive @entity11754 ( @entity11754 ), which occur at quiescent hepatocytes, not stem cells.
