The Cell Transformation Assay: A Historical Assessment of Current Knowledge of Applications in an Integrated Approach to Testing and Assessment for Non-Genotoxic Carcinogens

The history of the development of the cell transformation assays (CTAs) are described, providing an overview of in vitro cell transformation from its origin to the new transcriptomic-based CTAs. Application of this knowledge is utilised to address how the different types of CTAs variously addressing initiation and promotion, can be included on a mechanistic basis within the integrated approach to testing and assessment for non-genotoxic carcinogens. Building upon assay assessments targeting the key events in the IATA, we identify how the different CTA models can appropriately fit, following prescreening transcriptomic approaches, and assessment within the earlier key events of inflammation, immune disruption, mitotic signaling and cell injury and later key events of (sustained) proliferation and change in morphology leading to tumor formation. The complementary key biomarkers with respect to the precursor key events and respective CTAs are mapped, providing a structured mechanistic approach to represent the complexity of the (non-genotoxic) carcinogenesis process, and specifically their capacity to identify non-genotoxic carcinogenic chemicals in a human relevant IATA.

COLACCI Annamaria;  CORVI Raffaella;  OHMORI Kiyomi;  PAPARELLA Martin;  SERRA Stefania;  DA ROCHA CARRICO Iris;  VASSEUR Paule;  JACOBS Miriam; 

2024-01-04

MDPI

JRC133094

1422-0067 (online),   

https://www.mdpi.com/1422-0067/24/6/5659,    https://publications.jrc.ec.europa.eu/repository/handle/JRC133094,   

10.3390/ijms24065659 (online),