You are here:
Simulating Chemical-Induced Injury Using Virtual Hepatic Tissues
Citation:
SHAH, I. A., J. JACK, C. HAUGH, AND J. F. WAMBAUGH. Simulating Chemical-Induced Injury Using Virtual Hepatic Tissues . Presented at International Conference on Systems Biology 2010, Edinburugh, UK, October 12 - 15, 2010.
Impact/Purpose:
The objective of the Virtual Liver (v-LiverTM) is to develop an integrated in vitro and in silico framework to: (a) efficiently generate the plausible sequence of molecular, cellular and tissue events perturbed by a test chemical, and (b) quantitatively simulate the risk of these events in humans at environmentally relevant exposures. As a proof of concept we are focusing on 20 environmental chemicals that activate nuclear receptors (NR) and produce lesions of varying severity in rodents leading to cancer.
Description:
Chemical-induced liver injury involves a dynamic sequence of events that span multiple levels of biological organization. Current methods for testing the toxicity of a single chemical can cost millions of dollars, take up to two years and sacrifice thousands of animals. It is difficult to assess the health impact of long-term exposure to low levels of contaminants from animal studies. In vitro models offer a more efficient and humane alternative, however, translating chemical-induced molecular changes in cell cultures to clinical outcomes remains an open problem. A key research challenge in predicting many adverse outcomes is relating molecular changes with histopathologic lesions, which are the gold-standard for measuring toxicity.