کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10823547 | 1061895 | 2007 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Growth stimulation of UV-induced DNA damage retaining epidermal basal cells gives rise to clusters of p53 overexpressing cells
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کلمات کلیدی
phosphorylated H2AXp53SCCUV-DDBtPAUVBCPDsBCCγH2AX12-O-tetradecanoylphorbol-13-acetateMdm2 - MDM2DNA damage - آسیبDNAUltraviolet - اشعه فرابنفشUltraviolet radiation - اشعه ماوراء بنفشultraviolet B - اشعه ماوراء بنفش BMED - باminimal erythema dose - حداقل دوز اریتمCyclobutane pyrimidine dimers - دیررس پیریمیدین سیکلووبتانStem cell - سلول بنیادیprogenitor cell - سلول پیش از قاعدگیMouse - موشBasal cell carcinoma - کارسینوم سلول بازالSquamous cell carcinoma - کارسینوم سلول سنگفرشی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Ultraviolet (UV) radiation induces cyclobutane pyrimidine dimers (CPDs) and (6-4) photoproducts ((6-4)PPs) in DNA, which may give rise to clusters of cells expressing mutant p53 ('p53 patches') and eventually to skin carcinomas. We have previously reported that some basal cells in murine skin accumulate CPDs upon chronic low-level UV exposure and that these CPD-retaining basal cells (CRBCs) encompass epidermal stem and progenitor cells. Through replication of their damaged DNA CRBCs may become mutagenic foci from which tumors might form. We therefore investigated whether CRBCs may give rise to p53 patches after forced proliferation by repeated applications of 12-O-tetradecanoylphorbol-13-acetate (TPA). CRBCs, induced in SKH-1 hairless mice by chronic low-level UV exposure (70Â J/m2 daily for 40 days), disappeared in the TPA-induced epidermal hyperplasia within 2 weeks and numerous clusters of epidermal cells with overexpressed p53 appeared after 4 weeks. Neither mutant p53 patches nor any foci of pErk1/2-overexpressing cells that could have caused reactive wild type p53 expression were found. In skin exposed to a single high UV dose (2.8Â kJ/m2) no CRBCs occurred, and no p53 clusters were observed after TPA treatment. These experiments suggest that CRBCs are a prerequisite for the formation of clusters of p53-overexpressing cells. The high frequency of these clusters (about 1 for every 3 CRBCs) precludes mutations in p53 as a likely cause. We surmise that forced proliferation of CRBCs gives rise to genomic instability that is propagated in daughter cells and evokes wild type p53 overexpression, signifying a potentially oncogenic process different from classic UV carcinogenesis involving mutant p53.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: DNA Repair - Volume 6, Issue 11, 1 November 2007, Pages 1642-1650
Journal: DNA Repair - Volume 6, Issue 11, 1 November 2007, Pages 1642-1650
نویسندگان
Joanne G.W. Nijhof, Aat M. Mulder, Ewoud N. Speksnijder, Esther M. Hoogervorst, Leon H.F. Mullenders, Frank R. de Gruijl,