Radiocontrast media affect radiation-induced DNA damage repair in vitro and in vivo by affecting Akt signalling

Toulany, Mahmoud; Kehlbach, Rainer; Rodemann, H. Peter; Mozdarani, Hossein

doi:10.1016/j.radonc.2009.11.006

« Previous Next »Radiotherapy & Oncology
Volume 94, Issue 1 , Pages 110-116, January 2010

Radiocontrast media affect radiation-induced DNA damage repair in vitro and in vivo by affecting Akt signalling

Mahmoud Toulany
- Department of Radiation Oncology, University of Tuebingen, Germany
Rainer Kehlbach
- Department of Diagnostic Radiology, University of Tuebingen, Germany
H. Peter Rodemann
- Department of Radiation Oncology, University of Tuebingen, Germany
- Corresponding authors. Addresses: Division of Radiobiology and Molecular Environmental Research, Department of Radiation Oncology, Eberhard-Karls University Tuebingen, Roentgenweg 11, 72076 Tuebingen, Germany (H.Peter Rodemann); Department of Medical Genetics, School of Medical Sciences, Tarbiat Modares University, Tehran, P.O. Box 14115-111, Iran (H. Mozdarani).
Hossein Mozdarani
- Department of Medical Genetics, Tarbiat Modares University, Tehran, Iran
- Corresponding authors. Addresses: Division of Radiobiology and Molecular Environmental Research, Department of Radiation Oncology, Eberhard-Karls University Tuebingen, Roentgenweg 11, 72076 Tuebingen, Germany (H.Peter Rodemann); Department of Medical Genetics, School of Medical Sciences, Tarbiat Modares University, Tehran, P.O. Box 14115-111, Iran (H. Mozdarani).

Received 4 June 2009; received in revised form 19 October 2009; accepted 16 November 2009. published online 14 December 2009.

Abstract

Purpose

The study was performed to investigate cytogenetic effects of ionic and non-ionic radiocontrast media (RCM) meglumine, iohexol alone and in combination with irradiation in mouse bone marrow cells in vivo and in vitro.

Materials and methods

Micronuclei assay was performed in bone marrow cells (BMC) of Balb/C mice intraperitoneally injected with RCM in the presence or absence of whole-body irradiation of 50mGy. DNA repair (NHEJ) signalling and efficiency were analyzed by Western blot and γH2AX-foci assay in normal fibroblast HSF-7 and HUVEC cells.

Results

Both compounds reduced proliferation of BMC significantly. Concentrations of 0.5, 1 and 2ml/kg meglumine or iohexol significantly enhanced the frequency of micronucleated polychromatic erythrocytes (MnPCEs) at all doses of meglumine (p<0.01) and 2ml/kg of iohexol (p<0.05). Combined with irradiation meglumine at 0.5 and 1ml/kg led to a higher frequency of MnPCEs than iohexol/IR (p<0.05). Meglumine induced DNA-double strand breaks (DNA-DSB) in non-irradiated HSF and strongly increased residual DNA-DSB within 10min to 24h after irradiation with 200 or 400mGy (p<0.001). Iohexol did not induce DNA-DSB but blocked repair of radiation-induced DNA-DSB significantly (p<0.05). Meglumine blocked IR-induced Akt phosphorylation, phosphorylation of DNA-PKcs (S2056, T2609) and ATM (S1981). Iohexol only blocked phosphorylation of Akt and DNA-PKcs at S2056.

Conclusion

RCM result in clastogenic effects through interference intracellular signalling cascades involved in the regulation of non-homologous end-joining repair of DNA-DSB.

Keywords: Radiocontrast media, Ionizing radiation, Akt/DNA-PKcs, Micronuclei, γH2AX-foci