Influence of chronic low-dose/dose-rate high-LET irradiation from radium-226 in a human colorectal carcinoma cell line

Abstract

PurposeTo evaluate potential damages of chronic environmentally relevant low-dose/dose-rate high-LET irradiation from a naturally occurring alpha-emitting radionuclide (radium-226, 226Ra) on a human colorectal carcinoma HCT116 p53+/+ cell line. MethodsClonogenic survival assays and mitochondrial membrane potential (MMP) measurement with a sensitive fluorescent MMP probe JC-1 were performed in HCT116 p53+/+ cells chronically exposure to low doses/dose rates of 226Ra with high-LET. Comparisons were made with the human non-transformed keratinocyte HaCaT cell line and acute low-dose direct low-LET gamma radiation. Results and conclusionThe chronic low-dose/dose-rate alpha radiation (CLD/DRAR) did not reduce the clonogenic survival of HCT116 p53+/+ cells over the period of 70 days of exposure. Only one significant reduction in the HCT116 p53+/+ cells’ clonogenic survival was when cells were grown with 10,000mBq/mL 226Ra for 40 days and progeny cells were clonogenically assessed in the presence of 10,000mBq/mL 226Ra. The cumulative doses that cells received during this period ranged from 0.05 to 46.2mGy. The mitochondrial membrane potential (MMP) dropped initially in both HCT116 p53+/+ and HaCaT cells in response to CLD/DRAR. The MMP in HCT116 p53+/+ cells recovered more quickly at all dose points than and that in HaCaT cells until the end of the exposure period. The highest dose rate of 0.66mGy/day depolarized the HaCaT's mitochondria more consistently during the exposure period. The faster recovery status of the MMP in HCT116 p53+/+ cells than that in HaCaT cells was also observed after exposure to acute low-dose gamma rays. Overall, it was found that CLD/DRAR had little impact on the MMP of human colorectal cancer and keratinocyte cell lines.