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Toxicological Tipping Points: Using High-content Imaging Data from ToxCast (SOT 2020)
Citation:
Shah, I. Toxicological Tipping Points: Using High-content Imaging Data from ToxCast (SOT 2020). Society of Toxicology 59th Annual Meeting 2020, Anaheim, CA, March 15 - 19, 2020.
Impact/Purpose:
Abstract submitted for presentation at the Society of Toxicology 59th Annual Meeting in March 2020.
Description:
One of the key challenges to using in vitro data for risk assessment is differentiating adaptive from adverse cellular responses. We studied the effects of hundreds of chemicals in primary rat hepatocytes using high-content imaging (HCI) to measure dose and time-dependent perturbations in endoplasmic reticulum stress, mitochondrial function, lysosomal mass, steatosis, apoptosis, DNA texture, nuclear size and cell number. A new computational model is proposed to describe the dynamic response of the system as cell-state trajectories based on multidimensional HCI data streams. Cell-state trajectories produced by multiple concentrations chemicals showed resilience of the primary rat hepatocyte system in many cases, however, we also found "tipping points" in system recovery. Further analysis of trajectories identified dose-dependent transitions, or critical points, in system recovery. We believe that HCI can be used to reconstruct cell state trajectories and provide insights into adaptation and resilience for in vitro systems. This abstract does not reflect US EPA policy.