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Radiother Oncol. 2010 Jan;94(1):110-6. doi: 10.1016/j.radonc.2009.11.006. Epub 2009 Dec 11.

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

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1
Department of Radiation Oncology, University of Tuebingen, 72076 Tuebingen, Germany.

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 50 mGy. DNA repair (NHEJ) signalling and efficiency were analyzed by Western blot and gammaH2AX-foci assay in normal fibroblast HSF-7 and HUVEC cells.

RESULTS:

Both compounds reduced proliferation of BMC significantly. Concentrations of 0.5, 1 and 2 ml/kg meglumine or iohexol significantly enhanced the frequency of micronucleated polychromatic erythrocytes (MnPCEs) at all doses of meglumine (p<0.01) and 2 ml/kg of iohexol (p<0.05). Combined with irradiation meglumine at 0.5 and 1 ml/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 10 min to 24h after irradiation with 200 or 400 mGy (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.

PMID:
20005591
DOI:
10.1016/j.radonc.2009.11.006
[Indexed for MEDLINE]
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