TY - JOUR

T1 - Effect of Ba(II), Eu(III), and U(VI) on rat NRK-52E and human HEK-293 kidney cells in vitro

AU - Senwitz, Christian

AU - Butscher, Daniel

AU - Holtmann, Linus

AU - Vogel, Manja

AU - Steudtner, Robin

AU - Drobot, Björn

AU - Stumpf, Thorsten

AU - Barkleit, Astrid

AU - Heller, Anne

N1 - Funding Information: This work was funded by the German Federal Ministry of Education and Research (BMBF) under grant numbers 02NUK057A and 02NUK057B and is part of the joint project RADEKOR. L.H. acknowledges funding received from BMBF under grant number 02NUK057D

PY - 2024/5/1

Y1 - 2024/5/1

N2 - Heavy metals pose a potential health risk to humans when they enter the organism. Renal excretion is one of the elimination pathways and, therefore, investigations with kidney cells are of particular interest. In the present study, the effects of Ba(II), Eu(III), and U(VI) on rat and human renal cells were investigated in vitro. A combination of microscopic, biochemical, analytical, and spectroscopic methods was used to assess cell viability, cell death mechanisms, and intracellular metal uptake of exposed cells as well as metal speciation in cell culture medium and inside cells. For Eu(III) and U(VI), cytotoxicity and intracellular uptake are positively correlated and depend on concentration and exposure time. An enhanced apoptosis occurs upon Eu(III) exposure whereas U(VI) exposure leads to enhanced apoptosis and (secondary) necrosis. In contrast to that, Ba(II) exhibits no cytotoxic effect at all and its intracellular uptake is time-independently very low. In general, both cell lines give similar results with rat cells being more sensitive than human cells. The dominant binding motifs of Eu(III) in cell culture medium as well as cell suspensions are (organo-) phosphate groups. Additionally, a protein complex is formed in medium at low Eu(III) concentration. In contrast, U(VI) forms a carbonate complex in cell culture medium as well as each one phosphate and carbonate complex in cell suspensions. Using chemical microscopy, Eu(III) was localized in granular, vesicular compartments near the nucleus and the intracellular Eu(III) species equals the one in cell suspensions. Overall, this study contributes to a better understanding of the interactions of Ba(II), Eu(III), and U(VI) on a cellular and molecular level. Since Ba(II) and Eu(III) serve as inactive analogs of the radioactive Ra(II) and Am(III)/Cm(III), the results of this study are also of importance for the health risk assessment of these radionuclides.

AB - Heavy metals pose a potential health risk to humans when they enter the organism. Renal excretion is one of the elimination pathways and, therefore, investigations with kidney cells are of particular interest. In the present study, the effects of Ba(II), Eu(III), and U(VI) on rat and human renal cells were investigated in vitro. A combination of microscopic, biochemical, analytical, and spectroscopic methods was used to assess cell viability, cell death mechanisms, and intracellular metal uptake of exposed cells as well as metal speciation in cell culture medium and inside cells. For Eu(III) and U(VI), cytotoxicity and intracellular uptake are positively correlated and depend on concentration and exposure time. An enhanced apoptosis occurs upon Eu(III) exposure whereas U(VI) exposure leads to enhanced apoptosis and (secondary) necrosis. In contrast to that, Ba(II) exhibits no cytotoxic effect at all and its intracellular uptake is time-independently very low. In general, both cell lines give similar results with rat cells being more sensitive than human cells. The dominant binding motifs of Eu(III) in cell culture medium as well as cell suspensions are (organo-) phosphate groups. Additionally, a protein complex is formed in medium at low Eu(III) concentration. In contrast, U(VI) forms a carbonate complex in cell culture medium as well as each one phosphate and carbonate complex in cell suspensions. Using chemical microscopy, Eu(III) was localized in granular, vesicular compartments near the nucleus and the intracellular Eu(III) species equals the one in cell suspensions. Overall, this study contributes to a better understanding of the interactions of Ba(II), Eu(III), and U(VI) on a cellular and molecular level. Since Ba(II) and Eu(III) serve as inactive analogs of the radioactive Ra(II) and Am(III)/Cm(III), the results of this study are also of importance for the health risk assessment of these radionuclides.

KW - Chemical microscopy

KW - Cytotoxicity

KW - Heavy metal speciation

KW - Kidney cells

KW - Radionuclides

KW - TRLFS

UR - http://www.scopus.com/inward/record.url?scp=85187198197&partnerID=8YFLogxK

U2 - 10.1016/j.scitotenv.2024.171374

DO - 10.1016/j.scitotenv.2024.171374

M3 - Article

C2 - 38432374

AN - SCOPUS:85187198197

VL - 923

JO - Science of the Total Environment

JF - Science of the Total Environment

SN - 0048-9697

M1 - 171374

ER -