dc.contributor.author |
Sándor, Nikolett |
|
dc.contributor.author |
Schilling-Tóth, Boglárka |
|
dc.contributor.author |
Kis, Enikő |
|
dc.contributor.author |
Benedek, Anett |
|
dc.contributor.author |
Lumniczky, Katalin |
|
dc.contributor.author |
Sáfrány, Géza |
|
dc.contributor.author |
Hegyesi, Hargita |
|
dc.date.accessioned |
2015-11-12T13:13:30Z |
|
dc.date.available |
2015-11-12T13:13:30Z |
|
dc.date.issued |
2015 |
|
dc.identifier |
84945484200 |
|
dc.identifier.citation |
pagination=142-149;
journalVolume=793;
journalTitle=MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS; |
|
dc.identifier.uri |
http://repo.lib.semmelweis.hu//handle/123456789/2332 |
|
dc.identifier.uri |
doi:10.1016/j.mrgentox.2015.06.009 |
|
dc.description.abstract |
We have investigated the importance of GDF-15 (secreted cytokine belonging to the TGF-β superfamily) in low and high dose radiation-induced cellular responses. A telomerase immortalized human fibroblast cell line (F11hT) was used in the experiments. A lentiviral system encoding small hairpin RNAs (shRNA) was used to establish GDF-15 silenced cells. Secreted GDF-15 levels were measured in culture medium by ELISA. Cell cycle analysis was performed by flow cytometry. The experiments demonstrated that in irradiated human fibroblasts GDF-15 expression increased with dose starting from 100 mGy. Elevated GDF-15 expression was not detected in bystander cells. The potential role of GDF-15 in radiation response was investigated by silencing GDF-15 in immortalized human fibroblasts with five different shRNA encoded in lentiviral vectors. Cell lines with considerably reduced GDF-15 levels presented increased radiation sensitivity, while a cell line with elevated GDF-15 was more radiation resistant than wild type cells. We have investigated how the reduced GDF-15 levels alter the response of several known radiation inducible genes. In F11hT-shGDF-15 cells the basal expression level of CDKN1A was unaltered relative to F11hT cells, while GADD45A and TGF-β1 mRNA levels were slightly higher, and TP53INP1 was considerably reduced. The radiation-induced expression of TP53INP1 was lower in the silenced than in wild type fibroblast cells. Cell cycle analysis indicated that radiation-induced early G2/M arrest was abrogated in GDF-15 silenced cells. Moreover, radiation-induced bystander effect was less pronounced in GDF-15 silenced fibroblasts. In conclusion, the results suggest that GDF-15 works as a radiation inducible radiation resistance increasing factor in normal human fibroblast cells, acts by regulating the radiation-induced transcription of several genes and might serve as a radiation-induced early biomarker in exposed cells. |
|
dc.relation.ispartof |
urn:issn:1383-5718 |
|
dc.title |
Growth Differentiation Factor-15 (GDF-15) is a potential marker of radiation response and radiation sensitivity |
|
dc.type |
Journal Article |
|
dc.date.updated |
2015-11-12T10:32:31Z |
|
dc.language.rfc3066 |
en |
|
dc.identifier.mtmt |
2921599 |
|
dc.identifier.pubmed |
26520384 |
|