Synthesis and Preliminary Immunotoxicological Investigators on As-GSH conjugates

The central question to be addressed in this Pilot Project is whether glutathione conjugates, which we know are formed in vivo and in vitro, contribute to the differential toxicity of lymphoid cells resulting from differential exposures of these cells and tissues. AsIII(GS)3 and MMAIIIGS2 may be selectively delivered to other cells/tissues enriched in γ-GT (and GSH transporters), including the kidney and brain, providing a sound rationale for extending investigations into the role of these conjugates into other areas of arsenic toxicology. Dr. Tomat will lead the synthesis of these compounds, Dr. Burchiel will test the potential immunological toxicity while Dr. Monks explores the role of AsIII(GS)3 and MMAIIIGS2 in the neurotoxicological effects of arsenic. In addition, these investigators will collaborate with Dr. Cherrington with his expertise in drug transporters (MRPs) for detailed investigations on the PK and PD of AsIII(GS)3 and MMAIIIGS2. This pilot project represents a collaboration within the SWEHSC members between University of Arizona and University of New Mexico.  The Data obtained from these studies will be used to submit either a R21 application or a RO1 application) to the NIEHS.