Metals and low dose IR: Molecular effects of combined exposures using HepG2 cells as a biological model

[Display omitted] •Uranium mining wastes expose human and non-human biota to low dose IR and metals.•Genotoxic potential evaluation of low dose IR plus metals using in vitro tests.•Significant DNA damage and gene expression alterations in tumour suppressor genes.•Effects of IR plus metals complex exposures seen at very low doses.•Need to clarify the risks to review IR exposure limits to human/non-human biota. Uranium mining sites produce residues rich in metals and radionuclides, that may contaminate all environmental matrices, exposing human and non-human biota to low doses of ionizing radiation (LDIR) and to the chemical toxicity of several metals. To date, experimental and radio-epidemiological studies do not provide conclusive evidence of LDIR induced cancer. However, co-exposures (LDIR plus other contaminants), may increase the risks. To determine the potential for genotoxic effects in human cells induced by the exposure to LDIR plus metals, HEPG2 cells were exposed to different concentrations of a uranium mine effluent for 96 h. DNA damage was evaluated using the comet assay and changes in the expression of tumor suppressor and oncogenes were determined using qPCR. Results show that effluent concentrations higher than 5%, induce significant DNA damage. Also, a significant under-expression of ATM and TP53 genes and a significant overexpression of GADD45a gene was observed. Results show that the exposure to complex mixtures cannot be disregarded, as effects were detected at very low doses. This study highlights the need for further studies to clarify the risks of exposure to LDIR along with other stressors, to fully review the IR exposure risk limits established for human and non-human biota.