Abstract
Although nicotine has been implicated as a potential factor in the pathogenesis of human cancer, its mechanisms of action regarding cancer development remain largely unknown. HL-60 cells were used to investigate the effects of a short-term treatment with nicotine at concentrations found in the blood of smokers. The findings show that nicotine induces chromatin decondensation, histone H3 acetylation and up-regulation of the c-Jun transcription factor mRNA. This increase is inhibited by mecamylamine, a nicotinic receptor antagonist, suggesting that nicotine alters cellular function directly via nicotinic acetylcholine receptors and may then play a role in cell physiology and tumor promotion.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylation / drug effects
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Cell Nucleus / drug effects
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Cell Nucleus / genetics
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Cell Nucleus / metabolism
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Chromatin / drug effects*
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Chromatin / metabolism
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Dose-Response Relationship, Drug
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Gene Expression / drug effects
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HL-60 Cells
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Histones / metabolism
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Humans
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Immunoblotting
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Leukemia, Promyelocytic, Acute / genetics
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Leukemia, Promyelocytic, Acute / metabolism
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Leukemia, Promyelocytic, Acute / pathology
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Mecamylamine / pharmacology
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Nicotine / pharmacology*
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Nicotinic Antagonists / pharmacology
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Proto-Oncogene Proteins c-fos / genetics
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Proto-Oncogene Proteins c-jun / genetics*
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Time Factors
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Up-Regulation / drug effects
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Up-Regulation / genetics
Substances
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Chromatin
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Histones
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Nicotinic Antagonists
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Proto-Oncogene Proteins c-fos
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Proto-Oncogene Proteins c-jun
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RNA, Messenger
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Mecamylamine
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Nicotine