The capability for investigating mechanisms is based on methods that can be applied to the the intact animal and to the cellular level, and then extended to the molecular level. Effects identified at the cellular and molecular level can provide direction to and exploit the capabilities of the Environmental Molecular Sciences Laboratory in structural biology to solve specific problems in environmental health related to mechanisms of action. Capabilities in computational chemistry may be used as an initial step in hypothesis development to identify potential mechanisms involved in the induction of adverse effects and to help categorize the structural features that contribute to a particular mode of action. Over time, this approach will substantially improve the usefulness of quantitative structure-activity relationship approaches to identifying structural features that are important to diverse toxic responses. Unique expertise exists at PNNL in pharmacokinetics and metabolism, in carcinogenesis, and in the assessment of effects from exposure to electromagnetic fields.
Intended expansion is in the areas of reproductive and developmental toxicities.
The common bridge between these areas with cell signaling systems that are activated by neuroendocrine, paracrine, and autocrine factors that can be coupled with capabilities in toxicological screening allow and applied to a broad spectrum of problems. Within the area of experimental studies, we are characterizing EMF sources and dosimetry, and conducting studies of molecular and cellular biological responses, neurobehavioral and neuroendocrine effects, and classical characterization of carcinogenic, reproductive, and developmental effects. Classical and molecular epidemiology techniques verify experimental results or lead to hypotheses for study with experimental approaches. Cell Signaling Pathways and Cancer Molecular Toxicology. Technical capabilities in molecular biology focus on understanding the role of cell signaling systems in the development of disease produced by chemical and physical agents.