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

• Published in: Environmental research 2017-07, Vol.156, p.697-704
• Main Authors: Vo, Nguyen T.K., Sokeechand, Bibi S.H., Seymour, Colin B., Mothersill, Carmel E.
• Format: Article
• Language: English
• Subjects: CARCINOMAS; Cell Line; Cell Survival - radiation effects; Chronic low-dose alpha radiation; Clonogenic survival; Colorectal carcinoma; Colorectal Neoplasms; DOSE RATES; ENVIRONMENTAL SCIENCES; GAMMA RADIATION; Gamma Rays - adverse effects; HCT116 Cells; Humans; Keratinocytes - radiation effects; LOW DOSE IRRADIATION; Membrane Potential, Mitochondrial - radiation effects; MEMBRANES; MITOCHONDRIA; Mitochondrial membrane potential; Radium; Radium - toxicity; RADIUM 226
• ISSN: 0013-9351; 1096-0953
• DOI: 10.1016/j.envres.2017.04.041

To 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. Clonogenic 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. The 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. •Human colorectal carcinoma HCT116 p53+/+ and keratinocyte HaCaT cells were exposed to chronic low-dose/dose-rate alpha radiation (CLD/DRAR).•Unlike the HaCaT cells, HCT116 p53+/+ cells’ clonogenic survival and mitochondrial membrane potential (MMP) changed little upon CLD/DRAR.•Upon the mitochondrial membrane depolarization response induced by CLD/DRAR, HaCaT cells were more sensitive than HCT116 p53+/+.•Gamma radiation depolarized the mitochondria of both HaCaT and HCT116 p53+/+ in a dose-dependent manner.•The MMP in HCT116 p53+/+ could recover more quickly than that in HaCaT cells after an acute low-dose gamma irradiation challenge.