Chronic methylmercury (MeHg) exposure and toxicity continues to be of environmental concern. MeHg can cause severe neurological and developmental defects. Removal of MeHg from the body is the only effective remedy. Our recent work has shown that MeHg-L-cysteine is a substrate for the human amino acid transporters, LAT1 and LAT2, facilitating MeHg's rapid distribution in the body (Simmons-Willis et al. Biochem. Journal, in press). Recent work from our laboratory (Ballatori et al. Env. Health Perspectives, 106(5):267-271, 1998) demonstrated that N-acetylcysteine (NAC) added to drinking water of mice greatly increases the excretion of MeHg from the body. The molecular mechanism for this process was recently explored (Koh et al. Mol. Pharmacol., in press). This study indicates that a major renal organic anion transporter, Oat1, plays a significant role in MeHg removal from the kidney. The overall goals of the proposed work are to examine the mechanisms of MeHg elimination and determine the role of NAC as an antidote.
