Internal Threshold of Toxicological Concern (iTTC): Where We Are Today and What Is Possible in the Near Future.

The Threshold of Toxicological Concern (TTC) is a risk assessment tool for evaluating low-level exposure to chemicals with limited toxicological data. A next step in the ongoing development of TTC is to extend this concept further so that it can be applied to internal exposures. This refinement of TTC based on plasma concentrations, referred to as internal TTC (iTTC), attempts to convert the chemical-specific external NOAELs (in mg/kg/day) in the TTC database to an estimated internal exposure.

Suppression of ABCG2 mediated MDR in vitro and in vivo by a novel inhibitor of ABCG2 drug transport.

Cancer is a disease whose treatment is often limited due to the development of a phenomenon known as multidrug resistance (MDR). There is an immense demand for development of novel agents that can overcome the MDR in cancer. A group of transmembrane proteins called ATP-binding cassette transporters, present ubiquitously in the human body possesses a modular architecture, contributing immensely towards the development of MDR.

Trace metals alter DNA repair and histone modification pathways concurrently in mouse embryonic stem cells.

Exposure to metals alters gene expression, changes transcription rates or interferes with DNA repair mechanisms. We tested a hypothesis to determine whether in vitro acute metal exposure, with or without recovery, alters epigenetic pathways in mouse embryonic stem (mES) cells. We measured cell viability, total and histone protein production, changes in gene expression for differentiation and DNA repair, and histone lysine mono-methylation (H3K27me1), in differentiated cells.