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A Journal on Nuclear Medicine and Molecular Imaging
Affiliated to the and to the International Research Group of Immunoscintigraphy
Indexed/Abstracted in: Current Contents/Clinical Medicine, EMBASE, PubMed/MEDLINE, Science Citation Index (SciSearch), Scopus
Impact Factor 2,413
Online ISSN 1827-1936
AN OVERVIEW OF THE RADIOPHARMACOLOGY FIELD TO DATE
Friesen C. 1, Lubatschofski A. 2, Glatting G. 1, Debatin K. M. 2, Reske S. N. 1
1 Department of Nuclear Medicine University of Ulm, Ulm, Germany
2 University Children's Hospital, Ulm, Germany
Aim. Intravascular brachytherapy efficiently reduces vascular smooth muscle cell (SMC) proliferation, interstitial matrix production, vascular remodeling and restenosis rate after revascularization injury of coronary arteries. In this study we examined the molecular mechanisms of the cytotoxic effect of Re-188-mediated β-irradiation on a SMC culture model compared to that of paclitaxel.
Methods. SMC were irradiated with 1, 3, 10 and 30 Gy with Re-188 or treated with 1, 5, 10 µg/mL paclitaxel. After 24, 48 and 72 h, cell death, apoptosis pathways and cell cycle were examined.
Results. Irradiation and paclitaxel induced cell cycle arrest in G1. Dose-dependent cell death ranged from 40% at 1 Gy to 80% at 30 Gy irradiation, and induced in 45% of SMC treated with paclitaxel. Irradiation induced increasing rates of necrotic cell death up to 40% at 30 Gy. Activation of caspase-3 was detected, and poly(ADP-ribose)polymerase (PARP), the prototype substrate of caspases, was cleaved upon β-irradiation. In addition, β-irradiation-mediated apoptosis activated caspase-9, indicating that mitochondria were involved. Further-more, Bax was upregulated. However, upregulation of death-inducing ligands (DIL) or receptors (DIL-R) was not involved in β-irradiation-induced apoptosis in SMC. Similar to β-irradiation, the intrinsic mitochondrial apoptosis pathway was activated by paclitaxel.
Conclusion. These findings demonstrate that β-irradiation and paclitaxel induced apoptosis and activated apoptosis signaling pathways in SMC at several levels by triggering intrinsic mitochondrial but not external death receptor mediated pathways.