Influences of TP53 expression on cellular radiation response and its relevance to diagnostic biodosimetry for mission environmental monitoring.
TP53 is a transcriptional activator and regulates genomic instability and cellular responses to DNA damage in response to ionising radiation. The molecular mechanism behind p53-mediated responses, such as, apoptosis and genomic instability remains unclear. An in vitro model of biological effects to irradiation was established. In order to elucidate the functional role of TP53 under different stress-reaction pathways and identify possible biological indicators, p53 was stably transfected into HL-60 cells, which provides a p53 minus background. Significantly enhanced radiosensitivity and growth suppression were observed. G(2) accumulation was obtained. Radiation-induced apoptosis of HL-60 cells was significantly inhibited by TP53, indicating that, in the event of DNA damage, TP53 is able to prevent cell death of HL-60 leukaemia cells by sustaining an arrest of the cell cycle at G(2) phase. Further evidence will be presented to identify specific radiation-targeted genes or signals as possible biomarkers for early diagnosis of radiation damage as well as mission environmental monitoring.
Lu-Hesselmann
J
J
Bundeswehr Institute of Medical Occupational and Environmental Safety, Scharnhorststrasse 13, 10115 Berlin, Germany. Juxianluhesselmann@Bundeswehr.org
van Beuningen
D
D
Meineke
V
V
Franke
E
E
D001681:Biological Assay / Q000379:methods*; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000528:radiation effects*; D004307:Dose-Response Relationship, Radiation; D018922:HL-60 Cells; D006801:Humans; D011829:Radiation Dosage; D011834:Radiation Monitoring / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000378:metabolism*
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53