Evaluation of Genetic Susceptibility to Lead Intoxication Using Auto-Antibody Titers to Nervous System Proteins

Details

• Personal Author:
  Claudio L ; El-Fawal HA ; Waterman S
• Description:
  Lead intoxication is one of the most widespread environmentally-induced afflictions in the human population, yet many questions remain regarding the mechanisms of lead-induced neurotoxicity and its effects on immune responses. We hypothesize that lead may cause neurotoxicity by disruption of the blood-brain barrier (BBB). BBB dysfunction may expose antigenic proteins of the nervous system to circulating immune cells and produce changes in antibody titers in the serum. To explore this hypothesis, we have used two mouse strains which differ in the gene coding for 0-aminolevulinate dehydratase (ALAD), an enzyme implicated in susceptibility to lead intoxication in humans. Although the genetic difference we find in these mouse strains appears to be quantitative rather than qualitative, we show that this model parallels observations made in humans. Our findings show that mice with a duplication of the ALAD gene (strain D) accumulate more lead in their blood than mice with a single copy of the gene (strain C) when exposed to the same acute oral doses of lead during adulthood. Also, female mice showed higher titers than males. Assessment of BBB function with intravascular tracers and immunocytochemistry for extravasated serum proteins showed increased BBB permeability in strain D animals. These animals also showed higher antibody titers to many CNS proteins as compared to strain C. The data reported here suggest dysfunction of the BBB can occur in susceptible animals exposed during adulthood and that these animals are also more likely to produce higher auto-antibody titers to CNS components. [Description provided by NIOSH]
• Subjects:
  Animals Environmental Exposure Lead Lead Poisoning Nervous System Occupational Health Poisoning Safety
• Keywords:
  Animal Studies Environmental Exposure Genetic Factors Lead Poisoning Neurotoxic Effects Neurotoxicity
• ISSN:
  0731-9193
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Abstract or Summary
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  19
• Volume:
  15
• Issue:
  1
• NIOSHTIC Number:
  nn:20060114
• Citation:
  Toxicologist 1995 Mar; 15(1):19
• CAS Registry Number:
  Lead (CAS RN 7439-92-1)
• Federal Fiscal Year:
  1995
• Performing Organization:
  Mount Sinai School of Medicine, New York
• Peer Reviewed:
  False
• Start Date:
  19920701
• Source Full Name:
  The Toxicologist. Society of Toxicology 34th Annual Meeting, March 5-9,1995, Baltimore, Maryland
• End Date:
  19970630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:2965efa69683c7d48590bfcc84179a01ce8d70c5e8e7dcf3f245083d131252156a42f03b0ae34a7f81eeaa0576417d082f0399f983d9b9e3d6d31af862a5ace2
• Download URL:
  https://stacks.cdc.gov/view/cdc/224128/cdc_224128_DS1.pdf
• File Type:
  [PDF - 147.52 KB ]