8A Toxicological Application of Signal Transduction: Early Cellular Changes Can Be Indicative of Toxicity

Julie Vrana Miller1, Nicole Prince2, Julia A. Mouch2, and Jonathan W. Boyd3

1Cardno ChemRisk, Pittsburgh, PA, USA

2Department of Orthopaedics, West Virginia University School of Medicine, Morgantown, WV, USA

3Department of Orthopaedics and Department of Physiology and Pharmacology, West Virginia University School of Medicine, Morgantown, WV, USA

8.1 Introduction

The early cellular changes initiated by external stimuli (whether that be chemical, physical, or biological agents) can offer a host of information about the adaptive response and adverse effects related to individual chemical and mixture exposures. Notable examples of early cellular changes are perturbations of dynamic intracellular signaling networks and alterations in cellular bioenergetics, such as increased/decreased oxygen consumption or electron transport chain (ETC) uncoupling. Due to the interconnectivity of various effector proteins and biomolecules, activity at a distinct intracellular location can have consequences at distal locations. Furthermore, a true understanding of biological response to chemical exposures necessitates a better understanding of cellular changes in response to a range of concentrations (especially low‐dose exposures) and is essential to toxicity testing and chemical risk assessment. Finally, the ability to measure the rapid and dynamic cellular responses to exposure(s) is critical for an ...

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