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Molecular Circuits, Biological Switches, and Nonlinear Dose-Response Relationships
Melvin E. Andersen, Raymond S. H. Yang, C. Tenley French, Laura S. Chubb and James E. Dennison
Environmental Health Perspectives
Vol. 110, Supplement 6 (Dec., 2002), pp. 971-978
Published by: The National Institute of Environmental Health Sciences
Stable URL: http://www.jstor.org/stable/3455671
Page Count: 8
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Signaling motifs (nuclear transcriptional receptors, kinase/phosphatase cascades, G-coupled protein receptors, etc.) have composite dose-response behaviors in relation to concentrations of protein receptors and endogenous signaling molecules. "Molecular circuits" include the biological components and their interactions that comprise the workings of these signaling motifs. Many of these molecular circuits have nonlinear dose-response behaviors for endogenous ligands and for exogenous toxicants, acting as switches with "all-or-none" responses over a narrow range of concentration. In turn, these biological switches regulate large-scale cellular processes, e.g., commitment to cell division, cell differentiation, and phenotypic alterations. Biologically based dose-response (BBDR) models accounting for these biological switches would improve risk assessment for many nonlinear processes in toxicology. These BBDR models must account for normal control of the signaling motifs and for perturbations by toxic compounds. We describe several of these biological switches, current tools available for constructing BBDR models of these processes, and the potential value of these models in risk assessment.
Environmental Health Perspectives © 2002 The National Institute of Environmental Health Sciences