Comparing toxicological response in fish and human cells in vitro: A step towards enhanced understanding of stress biology across vertebrates

Both animal and human cells express highly conserved pathways in response to stress. Elucidating common pathways in different cell types is needed to harmonise the hazard and risk assessments adopting New Approach Methodologies (NAM), to protect both human and environmental health. However, direct comparison of cascades of responses in different species cell lines are scarce. Whilst for human cells a range of biomarker responses is being proposed to elucidate non-specific and specific toxicity of chemicals, there has been limited progress for fish cells. The need to learn from mammalian in vitro studies and adopt a common approach is being emphasized, despite inherent differences in maintenance and metabolic properties of these permanent cell lines. The assembled research team has significant previous experience regarding understanding relative sensitivity of fish and mammalian cells used concurrently evaluating cellular toxicity and genotoxicity following exposures to environmental chemicals.

Adopting integrated and interdisciplinary approaches which will include: (a) analytical (b) ‘biomarker’ responses and (c) modelling methodologies, this project aims to make a step change by comparing the relative sensitivity of permanent cell lines. The overall aims are: (a) enhance our ability of using human cell line-based assays to inform less explored fish endpoints; (b) adopt basic biology and molecular approaches to compare the (biomarker) responses for environmentally relevant chemicals; (c) elucidate how these cell types respond following acute and chronic exposure scenarios (d) explicate how the confounding factors and cell specific maintenance influence the biological responses.