Two studies will be conducted to answer the long-term objectives of evaluating the efficacy of succimer chelation for reducing neurotoxicity caused by moderate Pb exposure (Study 1) and whether caution should be used when Pb exposure continues during treatment (Study 2). Study 1 will utilize moderately Pb-exposed adult Rhesus monkeys that will be infused with a stable isotope tracer of Pb and then treated with succimer or placebo (control). They subsequently will be sacrificed to obtain brain samples and the stable isotope tracer concentrations of regions of these brains will be analyzed to meet the Specific Aims of determining I) the brain regional distribution of Pb in regions associated with cognitive function and II) the efficacy of succimer treatment for reducing brain Pb concentrations in these regions and whether succimer causes re- distribution of Pb into these regions. Study 2 will utilize moderately Pb-exposed juvenile Rhesus monkeys that will be simultaneously infused both intravenously nd orally with two stable isotope tracers of Pb and subsequently treated with succimer of placebo (control). Blood, feces, and urine will be collected and analyzed for the Pb isotope tracers to meet Specific Aim III) determining the effects of succimer treatment on the gastrointestinal absorption and retention of Pb.
| Smith, Donald; Strupp, Barbara J (2013) The scientific basis for chelation: animal studies and lead chelation. J Med Toxicol 9:326-38 |
| Rice, Sederick C; Vacek, Pamela M; Homans, Alan H et al. (2003) Comparative analysis of HPRT mutant frequency in children with cancer. Environ Mol Mutagen 42:44-9 |
| Cremin Jr, John D; Smith, Donald R (2002) In vitro vs in vivo Pb effects on brain protein kinase C activity. Environ Res 90:191-9 |
| Cremin Jr, J D; Luck, M L; Laughlin, N K et al. (2001) Oral succimer decreases the gastrointestinal absorption of lead in juvenile monkeys. Environ Health Perspect 109:613-9 |
| Cremin Jr, J D; Luck, M L; Laughlin, N K et al. (1999) Efficacy of succimer chelation for reducing brain lead in a primate model of human lead exposure. Toxicol Appl Pharmacol 161:283-93 |
