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- Bergdahl, Ingvar A., et al.
(författare)
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Lead binding to delta-aminolevulinic acid dehydratase (ALAD) in human erythrocytes
- 1997
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Ingår i: Basic and Clinical Pharmacology and Toxicology. - : Wiley. - 0901-9928. ; 81:4, s. 153-158
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Tidskriftsartikel (refereegranskat)abstract
- Over 99% of the lead present in blood is usually found in erythrocytes. To investigate the nature of this selective accumulation of lead in erythrocytes, the specific binding of lead to proteins in human erythrocytes was studied using liquid chromatography coupled to inductively coupled plasma mass spectrometry (LC-ICP-MS). The principal lead-binding protein had a mass of approximately 240 kDa, and adsorption to specific antibodies showed that protein was delta-aminolevulinic acid dehydratase (ALAD). Thus, the previous notion that lead in erythrocytes was bound primarily to haemoglobin has to be revised. Furthermore, in lead-exposed workers, the percentage of lead bound to ALAD was influenced by a common polymorphism in the ALAD gene. Specifically, in seven carriers of the ALAD2 allele, 84% of the protein-bound lead recovered was bound to ALAD compared to 81% in seven homozygotes for the ALAD1 allele whose erythrocytes were matched for blood-lead concentration. The small difference was statistically significant in Wilcoxon matched-pairs signed-rank test (P = 0.03). No ALAD allele-specific difference in ALAD-bound lead was found among 20 unexposed controls. Perhaps the difference in ALAD-bound lead can provide an explanation for the previously reported finding of higher blood-lead levels among carriers of the ALAD2 allele than among ALAD1 homozygotes in lead-exposed populations.
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| 2. |
- Bergdahl, Ingvar A
(författare)
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Lead in blood. ICP-MS studies of lead in plasma, blood and erythrocyte proteins
- 1997
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- An inductively coupled plasma mass spectrometry (ICP-MS) method for the determination of lead in blood plasma has been developed. The detection limit was below 0.1 microgram/liter, and the precision 5%. There was no significant difference between levels in plasma and serum. Studies of individuals with varying lead exposure showed that in the general population the plasma concentrations were less than 1% of the levels in blood, and up to a few percent in highly lead-exposed individuals. There was a non-linear relationship between blood- and plasma-lead concentrations. The non-linearity could be described by a model based on high-affinity erythrocyte lead-binding proteins with a limited binding capacity. The association was relatively close, with an inter-individual variation in plasma lead of 30% relative standard deviation at a given blood-lead concentration. Neither age, sex, current lead exposure, nor the polymorphism in the delta-aminolevulinic acid dehydratase (ALAD) gene affected the distribution of lead between cells and plasma. Moreover, lead-binding erythrocyte proteins were studied by gel-chromatography with ICP-MS detection. The studies showed that the protein with the highest affinity for lead was ALAD. Together with a smaller protein, with an apparent molecular mass of 45 kDa, it bound more than half of the lead in the erythrocytes. There was also a small lead-binding component; the quantity of lead bound to it its not known. Lead in erythrocytes appeared not to be bound to hemoglobin.
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