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

Abstract

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