کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3165928 1198861 2007 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Cigarette smoke condensate and dioxin suppress culture shock induced senescence in normal human oral keratinocytes
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی دندانپزشکی، جراحی دهان و پزشکی
پیش نمایش صفحه اول مقاله
Cigarette smoke condensate and dioxin suppress culture shock induced senescence in normal human oral keratinocytes
چکیده انگلیسی

SummaryThe aryl hydrocarbon receptor is a ligand activated transcription factor which regulates biological responses to a variety of environmental pollutants, such as dioxin (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) and cigarette smoke. The purpose of this study was to determine whether cigarette smoke condensate (CSC) is capable of activating the AHR in normal human oral keratinocytes (NHOK) and inhibiting their ability to senesce. Towards this end, NHOK were isolated from human subjects and were cultured in the presence or absence of either TCDD or CSC. While neither TCDD nor CSC treatments altered the lifespan of NHOK in culture, both were capable of suppressing a culture induced premature senescence as indicated by their ability to decrease the mRNA and protein levels of the senescence markers p16INK4a, p53 and p15INK4b. A role of the AHR in mediating these events is indicated by the observations that the TCDD and CSC-induced decreases in p15INK4b, p16INK4a and p53 expression was accompanied by a corresponding increase in the expression levels of the AHR target gene, CYP1A1. In addition, cotreatment with the AHR antagonist, 3′-methoxy-4′-nitroflavone (MNF) blocked the effects of TCDD and CSC on p53 and CYP1A1 expression. The findings of this study indicate that in NHOK, CSC is capable of altering a key cell fate decision, i.e., commitment to premature senescence, that is in part, dependent on the AHR. These results support the idea that progression of CSC-induced tumorigenesis may include an AHR-mediated inhibition of senescence that contributes to immortalization and agents that block the actions of the AHR may be effective components of novel cancer therapeutics.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Oral Oncology - Volume 43, Issue 7, August 2007, Pages 693–700
نویسندگان
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