Lead concentration in plasma as a biomarker of exposure and risk, and modification of toxicity by delta-aminolevulinic acid dehydratase gene polymorphism
Författare
Summary, in English
Blood lead concentration (B-Pb), the main biomarker of lead exposure and risk, is curvi-linearily related to exposure. We assessed plasma lead (P-Pb) as a marker for both lead exposure and toxic effects. We examined claims that delta-aminolevulinic acid dehydratase genotype (ALAD) can modify lead toxicity. In 290 lead-exposed and 91 unexposed Chinese workers, we determined P-Pb, B-Pb, urinary lead (U-Pb), AMD polymorphism (rs1800435, ALAD112; TaqMan assay), and also toxic effects on heme synthesis (blood zinc protoporphyrin and hemoglobin, urinary delta-aminolevulic acid), on the kidneys (urinary albumin, beta(2)microglobulin and N-acetyl-beta-D-glucosaminidase) and on the peripheral nervous system (sensory and motor conduction velocities). In exposed workers, median P-Pb was 4.10 (range 0.35-27) mu g/L, B-Pb 401 (110-950) mu g/L, and U-Pb 188 (22-590) mu g/g creatinine. P-Pb had a higher ratio between exposed and unexposed workers (median 39, range 18-110) than B-Pb (19, 15-36; p<0.001) and U-Pb (28, 15-36; p<0.001). All three biomarkers were associated with all toxic effects (P-Pb: r(s)= -0.10 to 0.79; B-Pb: r(s) = -0.08 to 0.75; all p <0.05). In the exposed workers, B-Pb and U-Pb were significantly higher (p = 0.04) in AIAD2 carriers (7% in the exposed population) than in ALAD1 homozygotes. P-Pb values were similar; ALAD1 homozygotes suffered higher kidney toxicity at the same P-Pb. Conclusions: (i) P-Pb has advantages over B-Pb as a biomarker of high Pb exposure, but it was not significantly better as an index of risk of toxicity. (ii) The ALAD genotype modifies toxicokinetics and toxicodynamics. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
Avdelning/ar
Publiceringsår
2013
Språk
Engelska
Sidor
102-109
Publikation/Tidskrift/Serie
Toxicology Letters
Volym
221
Issue
2
Dokumenttyp
Artikel i tidskrift
Förlag
Elsevier
Ämne
- Pharmacology and Toxicology
Nyckelord
- Lead
- Occupational exposure
- Plasma
- delta-Aminolevulinic acid
- dehydratase gene
- Gene-environment interaction
Status
Published
ISBN/ISSN/Övrigt
- ISSN: 1879-3169