Einflussnahme von TGFβ auf die Strahlensensibilität lymphoblastoider Zellen

Influence of TGFβ on the radiosensibility of lymphoblastiod cells

by Katarina Springer
Doctoral thesis
Date of Examination:2016-04-14
Date of issue:2016-04-11
Advisor:PD Dr. Hendrik Wolff
Referee:PD Dr. Jochen Gaedcke
Referee:Prof. Dr. Thomas Meyer
Persistent Address: http://dx.doi.org/10.53846/goediss-5605

 

 

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Abstract

English

In this thesis 48 commercially purchased lymphoblastoid cell lines (LCLs) were used to investigate the effects of 1771 gene polymorphisms out of 23 candidate genes on genomic damages following various treatments. Therefore the LCLs were either incubated with 5 ng/ml TGFβ1, exposed to irradiation of 3 Gy or underwent a combined treatment (5 ng/ml TGFβ1 16 hours before 3 Gy irradiation) and were compared to an untreated sample. After an incubation period of 28 hours at 37°C and 5 % CO2 the micronucleus test was performed to make the chromosomal damages visible under the microscope. 14 cell lines were also to be reproduced in analogous form a few weeks later. A significant increase in chromosomal damage in the form of nucleoplasmic bridges (NPB) and micronuclei (MNi) was shown. Between the treatment conditions 3 Gy irradiation without TGFβ1 and 3 Gy irradiation with TGFβ1 a significant increase of NPB (p > 0,005) and MNi (p = 0,04) could be shown. Between the replicates a statistical significance of p ≤ 0,05 was found only in the NPB. In the majority of the candidate genes TGFβ1 showed no significant effect on the radiosensibility of the LCLs. However, in some genes an increase of radiosensibility has been observed when the variant allele was present (rs 4986852 in BRCA1, rs1800734 in MLH1, rs2020911 and rs2710163 in MSH6, rs893473 in SMAD3, rs11466445 in TGFBR1). Also the opposite effect, a decrease of radiosensibility under the TGFβ1 treatment was detected in presence of the variant allele (rs25487 in XRCC1, rs12900401 in SMAD3, rs17663887 in SMAD4).
Keywords: radiosensibility; lymphoblastoid cell lines; micronuleus test; single-nucleotide polymorphism; TGFβ pathway
Schlagwörter: Mikrokerntest; Strahlensensibilität; Einzelnukleotid Polymorphismus; lymphoblastoide Zellen; TGFβ Signalweg
 
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