Lead concentration in plasma as a biomarker of exposure and risk, and modification of toxicity by δ-aminolevulinic acid dehydratase gene polymorphism.
Toxicol Lett
; 221(2): 102-9, 2013 Aug 14.
Article
in En
| MEDLINE
| ID: mdl-23792432
ABSTRACT
UNLABELLED 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 δ-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), ALAD polymorphism (rs1800435, ALAD1/2; TaqMan assay), and also toxic effects on heme synthesis (blood zinc protoporphyrin and hemoglobin, urinary δ-aminolevulic acid), on the kidneys (urinary albumin, ß2-microglobulin and N-acetyl-ß-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)µg/L, B-Pb 401 (110-950)µg/L, and U-Pb 188 (22-590)µg/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 rS=-0.10 to 0.79; B-Pb rS=-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 ALAD2 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.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Polymorphism, Genetic
/
Biomarkers
/
Porphobilinogen Synthase
/
Lead
Type of study:
Etiology_studies
/
Observational_studies
/
Risk_factors_studies
Limits:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Asia
Language:
En
Journal:
Toxicol Lett
Year:
2013
Document type:
Article