Abstract
We examined the p53 response following acute exposure of mice to the colon-specific carcinogen azoxymethane (AOM). No overall induction of p53-regulated genes was observed in the mouse colon, and only a small subpopulation of apoptotic colonocytes showed increased Bax staining. In contrast, the liver showed dramatic increases in p53-regulated gene expression. Subdued p53 gene activation in the colon did not appear to result from a lack of p53 stabilization, but did correspond to a drop in the expression of its transcriptional co-activator, p300. We propose that inefficient gene activation by p53 in the colon contributes to the organotrophic effects of AOM.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis / drug effects
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Carcinogens / toxicity*
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Cells, Cultured
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Colon / drug effects
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Colon / metabolism*
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Colonic Neoplasms / chemically induced*
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Colonic Neoplasms / pathology
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DNA Damage
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E1A-Associated p300 Protein
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Epithelial Cells / chemistry
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Epithelial Cells / drug effects
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Epithelial Cells / metabolism
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Gene Expression Regulation, Neoplastic / drug effects*
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Genes, p53 / genetics*
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Immunoblotting
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Immunohistochemistry
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Mice
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Mice, Inbred A
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Nuclear Proteins / genetics*
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Nuclease Protection Assays
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Proteins / chemistry
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Proteins / isolation & purification
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins c-bcl-2*
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RNA, Messenger / biosynthesis
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RNA, Messenger / isolation & purification
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Trans-Activators / genetics*
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Transcriptional Activation
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bcl-2-Associated X Protein
Substances
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Bax protein, mouse
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Carcinogens
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Nuclear Proteins
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Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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RNA, Messenger
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Trans-Activators
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bcl-2-Associated X Protein
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E1A-Associated p300 Protein
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Ep300 protein, mouse