کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8456508 | 1548603 | 2013 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Smad7 foci are present in micronuclei induced by heavy particle radiation
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کلمات کلیدی
HZEDSBBNLNSRLDDRTGFβpSmad2IRIFSmad7ataxia telangiectasia mutated - Ataxia telangiectasia جهش یافته استROS - ROSBrookhaven National Laboratory - آزمایشگاه ملی بروکلینLET - اجازه دهیدLinear Energy Transfer - انتقال انرژی خطیHigh LET radiation - تابش بالا LETionizing radiation - تابش یوننده یا پرتوهای یونیزانTransforming Growth Factor Beta - تبدیل بتا فاکتور رشدDNA repair - ترمیم DNAATM - خودپردازmicronuclei - ریزهستک یا میکرونوکلئوس double strand break - شکست دو رشتهDNA damage response - واکنش به آسیب DNA Reactive oxygen species - گونههای فعال اکسیژن
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
DNA damage and reactive oxygen species (ROS) generated by ionizing radiation (IR) activate DNA damage response (DDR) and cytokine signaling pathways, including double strand break (DSB) repair and TGFβ/Smad signaling pathway. Proteins assembled at IR-induced DSB sites can be visualized as foci, including γH2AX, 53BP1, ATM and ATF2. Unrepaired DSBs are thought to be one origin of micronuclei (MN), an indicator of genotoxic stress and chromosomal instability. Studies have detected γH2AX in IR-induced MN, indicating the presence of DSB in MN. Previously we reported that TGFβ downstream proteins Smad7 and phospho-Smad2 (pSmad2) co-localized with DDR proteins following radiation. Here we studied the status of Smad7 and pSmad2 in MN post high linear energy transfer (LET) radiation in human normal and cancerous cells. We observed γH2AX foci in IR-induced MN, whereas 53BP1 and ATF2 were absent. Interestingly, Smad7 foci, but not pSmad2, were detectable in both spontaneous and IR-induced MN. We compared the effect of particle track structures on the yield of MN using 5.6 MeV/u boron (B) and 600 MeV/u iron (Fe) particles with similar LET (200 and 180 keV/μm, respectively) in human fibroblasts. The frequency of MN induced by B was lower than that by Fe particles, albeit the proportion of Smad7-positive to Smad7-negative MN remained constant. An increased frequency of spontaneous MN, with slightly higher ratio of Smad7 or γH2AX positive, was found in human prostate cancer cells (PC3) compared to normal cells. 24 h after 1 Gy of Fe particles exposure, the yield of MN increased, and the majority (â¼70%) carried γH2AX and Smad7. Phospho-ATM (Ser1981) foci were found in both spontaneous and IR-induced MN in PC3 cells, displaying a much lower frequency compared to γH2AX and Smad7. Our data suggest a unique role of Smad7 in IR-induced MN formation, which may associate with DNA repair, apoptosis and genomic instability.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Mutation Research/Genetic Toxicology and Environmental Mutagenesis - Volume 756, Issues 1â2, 30 August 2013, Pages 108-114
Journal: Mutation Research/Genetic Toxicology and Environmental Mutagenesis - Volume 756, Issues 1â2, 30 August 2013, Pages 108-114
نویسندگان
Minli Wang, Janapriya Saha, Francis A. Cucinotta,