Genetic Determinants of Sensitivity to Beryllium in Mice

Details

• Personal Author:
  Gordon T ; Nadas A ; RubinEM ; Sorrentino C ; Tarantino-Hutchison LM ; Tinkle SS ; Weston A ; Zhu YW
• Description:
  Chronic beryllium disease (CBD), an irreversible, debilitating granulomatous lung disease is caused by exposure to beryllium. This occupational hazard occurs in primary production and machining of Be-metal, BeO, beryllium containing alloys, and other beryllium products. CBD begins as an MHC Class II-restricted, T(H)1 hypersensitivity, and the Human Leukocyte Antigen, HLA-DPB1E(69), is associated with risk of developing CBD. Because inbred strains of mice have not provided good models of CBD to date, three strains of HLA-DPB1 transgenic mice in an FVB/N background were developed; each contains a single allele of HLA-DPB1 that confers a different magnitude of risk for chronic beryllium disease: HLA-DPB1*0401 (OR approximate to 0.2), HLA-DPB1*0201 (OR approximate to 3), and HLA-DPB1*1701 (OR approximate to 46). The mouse ear swelling test ( MEST) was employed to determine if these different alleles would support a hypersensitivity response to beryllium. Mice were first sensitized on the back and subsequently challenged on the ear. In separate experiments, mice were placed into one of three groups (sensitization/challenge): C/C, C/Be, and Be/Be. In the HLA-DPB1*1701 mice, the strain with the highest risk transgene, the Be/Be group was the only group that displayed significant maximum increased ear thickness of 19.6% +/- 3.0% over the baseline measurement (p < 0.05). No significant changes were observed in the other transgenic strains for any treatment condition. In addition, inter-strain differences in response to beryllium in seven inbred strains were investigated through use of the MEST, these included: FVB/N, AKR, Balb/c, C3H/HeJ, C57/BL6, DBA/2, and SJL/J. The FVB/N strain was least responsive, while the SJL/J and C57/BL6 strains were the highest responders. Our results suggest that the HLA-DPB1*1701 transgene product is an important risk factor for induction of the beryllium-sensitive phenotype. This model should be a useful tool for investigating beryllium sensitization. [Description provided by NIOSH]
• Subjects:
  Antigens Beryllium Biochemistry Biological Factors Chemistry Dust Environmental Monitoring Hazardous Substances Hypersensitivity Laboratories Lung Lung Diseases Manufacturing And Industrial Facilities Metals Metal Workers Occupational Diseases Occupational Exposure Occupational Health Poisoning Respiratory System Respiratory Tract Diseases Safety Workplace

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• Keywords:
  Author Keywords: Beryllium Beryllium-disease Biochemical-analysis Biohazards Biological-effects Biological-factors Biological-function Biological-systems Chemical-hypersensitivity Chemical-manufacturing-industry Chemical-properties Chronic Beryllium Disease Exposure-assessment Exposure-levels Exposure-methods Health-hazards Inhalation-studies Laboratory-animals Laboratory-testing Lung-disease Lung-disorders Lung-irritants Metal-dusts Metal-fumes Metal-poisoning Metal-workers Metalworking Metalworking-industry Mouse Model Occupational-diseases Occupational-exposure Occupational-hazards Occupational-respiratory-disease Pulmonary-disorders Pulmonary-system Pulmonary-system-disorders Statistical-analysis Work-environment Work-practices Worker-health

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• ISSN:
  1547-691X
• Document Type:
  Text
• Genre:
  Journal Article
• Place as Subject:
  California ; New York ; North Carolina ; OSHA Region 2 ; OSHA Region 3 ; OSHA Region 4 ; OSHA Region 9 ; West Virginia
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  DRDS - Division of Respiratory Disease Studies ; HELD - Health Effects Laboratory Division
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  130-135
• Volume:
  6
• Issue:
  2
• NIOSHTIC Number:
  nn:20035787
• Citation:
  J Immunotoxicol 2009 Jun; 6(2):130-135
• Contact Point Address:
  Terry Gordon, PhD, NYU School of Medicine, 57 Old Forge Rd., Tuxedo, NY 10987
• Email:
  terry.gordon@nyumc.org
• CAS Registry Number:
  Beryllium (CAS RN 7440-41-7)
• Federal Fiscal Year:
  2009
• NORA Priority Area:
  Manufacturing
• Peer Reviewed:
  True
• Source Full Name:
  Journal of Immunotoxicology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:23bc878857f4cb3bc976fca80bcfae5d4c4d0c2cb63e3a6832b617c1dc54d15713e838dfded05fc54697c85a8d873120b65857c36d8a2558e9f833f9b06ab8a2
• Download URL:
  https://stacks.cdc.gov/view/cdc/187516/cdc_187516_DS1.pdf
• File Type:
  [PDF - 907.08 KB ]