Work

Am/Cm(III) and DTPA/LIHOPO interactions with renal cells in vitro studied by bioassays, luminescence spectroscopy, and microdosimetry

Year: 2025

Type: article

Abstract: Incorporation of trivalent actinide ions into the human body holds inherent significant chemo- and radiotoxic risks. This necessitates effective decorporation strategies based on knowledge of the underlying mechanisms of molecular and cellular actinide interactions. For americium and curium (Am/Cm), that state of knowledge is low. Therefore, this study represents the first comprehensive investigation on the impact of 243 Am and the decorporation agents CaNa 3 -DTPA (DTPA) and 3,4,3-LI(1,2-HOPO) (LIHOPO) on rat kidney cells. Following in vitro exposition experiments, the analyses included various cell-based bioassays complemented by microdosimetric calculations, cellular uptake measurements, and Am/Cm speciation studies. Results demonstrate that cell viability and morphology are severely impaired and cell death processes, oxidative stress, and DNA double strand breaks are induced in a time- and concentration-dependent manner after Am exposure. Furthermore, α-particle radiation from extracellular Am in the cell culture medium is the main contributor to radiation dose. There is evidence that ROS and caspase 3/7 induction are most likely related to Am chemotoxicity, whereas DNA double strand breaks mainly depend on extracellular Am radiotoxicity. DTPA leads to the formation of largely cell impermeable AmDTPA 2- significantly reducing intracellular metal uptake and cytotoxicity. In contrast, LIHOPO forms highly cell permeable AmLIHOPO - enhancing intracellular metal uptake and cytotoxicity under steady-state conditions. This study provides useful insights for radiation protection against Am/Cm and may help to explain observations in clinical trials with new potential decorporation agents. • First EC 50 values of kidney cells exposed to 243 Am for 24 h in vitro. • DTPA reduces intracellular 243 Am uptake as well as cytotoxic impairments in vitro. • LIHOPO causes increased 243 Am accumulation and cellular stress response in vitro. • Alpha-radiation from extracellular 243 Am is main contributor to radiation dose. • First spectroscopic characterization of intracellular 243 Am-LIHOPO complex.

Source: Ecotoxicology and Environmental Safety

DOI: 10.1016/j.ecoenv.2025.119445