# Technology-Critical Element Exposure Reveals Divergent Toxicity in Different Human Cells Despite Comparable Uptake

## TL;DR

This study shows that different human cells react very differently to the same technology-critical elements, even when they absorb similar amounts.

## Contribution

The study reveals that toxicity of TCEs is not directly linked to uptake levels and highlights divergent cellular responses.

## Key findings

- Normal BJ fibroblasts were vulnerable to TCEs, while HepG2 cells were highly resistant.
- Toxicity differences correlated with opposing antioxidant responses in the two cell types.
- Low concentrations of cerium (III) nitrate stimulated HepG2 cell proliferation.

## Abstract

The increasing use of Technology-Critical Elements (TCEs) in modern technology has led to widespread environmental release, raising questions about their biological effects, as emerging evidence suggests significant toxicity. We investigated the effects of three technology-critical elements, Indium oxide (In2O3), Lanthanum nitrate hexahydrate (La(NO3)3·6H2O) and Cerium(III) nitrate hexahydrate (Ce(NO3)3·6H2O), on human dermal fibroblasts (BJ) and hepatocarcinoma cells (HepG2), assessing their uptake, impact on viability, and induced cellular stress responses, quantified by markers of inflammation, oxidative stress, and membrane damage. Our results show a strong differential susceptibility: normal BJ fibroblasts proved vulnerable, whereas HepG2 cells were highly resistant. This divergence occurred despite substantial and comparable accumulation of all three TCEs in both cell lines, indicating that toxicity is uncoupled from the magnitude of the uptake. Mechanistically, the differential toxicity correlated strongly with opposing antioxidant responses. Additionally, low concentrations of cerium (III) nitrate (12.5–50 µg/mL) uniquely stimulated the proliferation of HepG2 cells (up to 129% of control). While these findings identify multiple mechanistic hazards regarding the potential of low-level technology-critical element exposure, they must be interpreted cautiously and warrant further investigation in more complex biological models.