# Finding a Direct Method for a Dynamic Process: The DD (Direct and Dynamic) Cell-Tox Method

**Authors:** Eneko Madorran, Lidija Kocbek Šaherl, Mateja Rakuša, Iztok Takač, Miha Munda

PMC · DOI: 10.3390/ijms25105133 · International Journal of Molecular Sciences · 2024-05-09

## TL;DR

This paper introduces a new cell-based toxicity method that tracks multiple cell responses to better assess the effects of toxic substances.

## Contribution

The DD Cell-Tox method captures dynamic cell responses (death, division, viability) for more accurate toxicity assessment.

## Key findings

- The method showed good accuracy compared to existing toxicity assessment techniques.
- It provided more representative information on toxic effects by considering diverse cellular responses.
- The method was successfully tested on monoculture and coculture models with various toxicants.

## Abstract

The main focus of in vitro toxicity assessment methods is to assess the viability of the cells, which is usually based on metabolism changes. Yet, when exposed to toxic substances, the cell triggers multiple signals in response. With this in mind, we have developed a promising cell-based toxicity method that observes various cell responses when exposed to toxic substances (either death, division, or remain viable). Based on the collective cell response, we observed and predicted the dynamics of the cell population to determine the toxicity of the toxicant. The method was tested with two different conformations: In the first conformation, we exposed a monoculture model of blood macrophages to UV light, hydrogen peroxide, nutrient deprivation, tetrabromobisphenol A, fatty acids, and 5-fluorouracil. In the second, we exposed a coculture liver model consisting of hepatocytes, hepatic stellate cells, Kupffer cells, and liver sinusoidal endothelial cells to rifampicin, ibuprofen, and 5-fluorouracil. The method showed good accuracy compared to established toxicity assessment methods. In addition, this approach provided more representative information on the toxic effects of the compounds, as it considers the different cellular responses induced by toxic agents.

## Linked entities

- **Chemicals:** hydrogen peroxide (PubChem CID 784), tetrabromobisphenol A (PubChem CID 6618), fatty acids (PubChem CID 264), 5-fluorouracil (PubChem CID 3385), rifampicin (PubChem CID 135398735), ibuprofen (PubChem CID 3672)

## Full-text entities

- **Diseases:** toxicity (MESH:D064420)
- **Chemicals:** hydrogen peroxide (MESH:D006861), tetrabromobisphenol A (MESH:C020806), fatty acids (MESH:D005227), rifampicin (MESH:D012293), ibuprofen (MESH:D007052), 5-fluorouracil (MESH:D005472)

## Full text

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## Figures

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## References

52 references — full list in the complete paper: https://tomesphere.com/paper/PMC11120653/full.md

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Source: https://tomesphere.com/paper/PMC11120653