|
|
|
|
Long-term epigenetic effects of exposure to low doses of 56Fe in the mouse lung
|
|
|
|
|
|
|
|
نویسنده
|
nzabarushimana e. ,miousse i.r. ,shao l. ,chang j. ,allen a.r. ,turner j. ,stewart b. ,raber j. ,koturbash i.
|
|
منبع
|
journal of radiation research - 2014 - دوره : 55 - شماره : 4 - صفحه:823 -828
|
|
چکیده
|
Despite significant progress,the long-term health effects of exposure to high charge (z) and energy (e) nuclei (hzes) and the underlying mechanisms remain poorly understood. mouse studies show that space missions can result in pulmonary pathological states. the goal of this study was to evaluate the pro-fibrotic and pro-carcinogenic effects of exposure to low doses of heavy iron ions (56fe) in the mouse lung. exposure to 56fe (600 mev; 0.1,0.2 and 0.4 gy) resulted in minor pro-fibrotic changes,detected at the beginning of the fibrotic phase (22 weeks post exposure),which were exhibited as increased expression of chemokine ccl3,and interleukin il4. epigenetic alterations were exhibited as global dna hypermethylation,observed after exposure to 0.4 gy. cadm1,cdh13,cdkn1c,mthfr and sfrp1 were significantly hypermethylated after exposure to 0.1 gy,while exposure to higher doses resulted in hypermethylation of cdkn1c only. however,expression of these genes was not affected by any dose. congruently with the observed patterns of global dna methylation,dna repetitive elements were hypermethylated after exposure to 0.4 gy,with minor changes observed after exposure to lower doses. importantly,hypermethylation of repetitive elements coincided with their transcriptional repression. the findings of this study will aid in understanding molecular determinants of pathological states associated with exposure to 56fe,as well as serve as robust biomarkers for the delayed effects of irradiation. further studies are clearly needed to investigate the persistence and outcomes of molecular alterations long term after exposure. © 2014 the author.
|
|
کلیدواژه
|
DNA methylation; epigenetics; heavy iron ions; lung cancer; pulmonary fibrosis; repetitive elements
|
|
آدرس
|
department of environmental and occupational health,college of public health,university of arkansas for medical sciences,4301 west markham street,little rock,72205-7199,ar, United States, department of environmental and occupational health,college of public health,university of arkansas for medical sciences,4301 west markham street,little rock,72205-7199,ar, United States, division of radiation health,department of pharmaceutical sciences,university of arkansas for medical sciences,4301 west markham street,little rock,72205-7199,ar, United States, division of radiation health,department of pharmaceutical sciences,university of arkansas for medical sciences,4301 west markham street,little rock,72205-7199,ar, United States, division of radiation health,department of pharmaceutical sciences,university of arkansas for medical sciences,4301 west markham street,little rock,72205-7199,ar, United States, department of behavioral neuroscience,onprc,oregon health and science university,3181 s.w. sam jackson park rd,portland,97239-3098,or, United States, department of behavioral neuroscience,onprc,oregon health and science university,3181 s.w. sam jackson park rd,portland,97239-3098,or, United States, department of behavioral neuroscience,onprc,oregon health and science university,3181 s.w. sam jackson park rd,portland,97239-3098,or,united states,department of neurology,onprc,oregon health and science university,3181 s.w. sam jackson park rd,portland,97239-3098,or,united states,division of cancer biology and radiobiology,division of neuroscience,oregon health and science university,3181 s.w. sam jackson park rd,portland,97239-3098,or, United States, department of environmental and occupational health,college of public health,university of arkansas for medical sciences,4301 west markham street,little rock,72205-7199,ar, United States
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
Authors
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|