A novel mathematical model describing adaptive cellular drug metabolism and toxicity in the chemoimmune system.

ABSTRACT: Cells cope with the threat of xenobiotic stress by activating a complex molecular network that recognizes and eliminates chemically diverse toxic compounds. This "chemoimmune system" consists of cellular Phase I and Phase II metabolic enzymes, Phase 0 and Phase III ATP Binding Cassette (ABC) membrane transporters, and nuclear receptors regulating these components. In order to provide a systems biology characterization of the chemoimmune network, we designed a reaction kinetic model based on differential equations describing Phase 0-III participants and regulatory elements, and characterized cellular fitness to evaluate toxicity. In spite of the simplifications, the model recapitulates changes associated with acquired drug resistance and allows toxicity predictions under variable protein ex

SUBMITTER: Toth A 

PROVIDER: S-EPMC4338831 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature