Superfund Research Program

Improving Ecological Risk Assessment: Development and Application of Methods to Determine the Bioavailability of Contaminants in Aquatic Sediments - New Bedford SF Site

Project Leader: James P. Shine
Grant Number: P42ES005947
Funding Period: 1995 - 2006

Project-Specific Links

Final Progress Reports

Year:   2005  1999 

Examination of the ALAD genotype in lead-exposed individuals has been completed. Project work demonstrating that the variant ALAD allele (ALAD-2) interacts with the vitamin D receptor polymorphism to alter lead incorporation into bones has also been completed. The researchers have also shown that physiologic and health outcomes of low level lead exposure are affected by the ALAD variant allele. This work combines to suggest that the ALAD variant protein directly alters the kinetics of lead absorption and/or distribution in the body. The initial hypothesis that ALAD-2 will be protective of lead toxicity by sequestering lead from sensitive sites of neurotoxic action is supported by the findings that lead binds to hemoglobin more tightly in the presence of the ALAD variant protein (ALAD-2). When lead is tightly bound to hemoglobin, it is not available as a neurotoxin because it cannot move out of the red cell fraction of blood to other cells such as nerve cells. It is also not readily incorporated into either trabecular bone or cortical bone where it could be stored for release at some future time during periods of enhanced resorption of bone as is characteristic during pregnancy, lactation, and in osteoporosis. The second hypothesis that ALAD genotype provides a useful biomarker of the effectiveness of chelation therapy used in the treatment of lead poisoning, is supported by findings showing that ALAD-2 individuals may respond less-well to chelating agents such as dimercaptosuccinic acid. An additional finding showed that ALAD-2 individuals exposed to environmental lead might demonstrate an increase in renal dysfunction.