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delta-Aminolevulinic acid dehydratase genotype modifies four hour urinary lead excretion after oral administration of dimercaptosuccinic acid.
Occup Environ Med. 1997 Apr; 54(4):241-6.OE

Abstract

OBJECTIVES

Previous research suggests that binding of lead by delta-aminolevulinic acid dehydratase (ALAD) may vary by ALAD genotype. This hypothesis was tested by examining whether ALAD genotype modifies urinary lead excretion (DMSA chelatable lead) after oral administration of dimercaptosuccinic acid (DMSA).

METHODS

57 South Korean lead battery manufacturing workers were given 5 mg/kg oral DMSA and urine was collected for four hours. Male workers were randomly selected from two ALAD genotype strata (ALAD1-1, ALAD1-2) from among all current workers in the two plants (n = 290). Subjects with ALAD1-1 (n = 38) were frequency matched with subjects with ALAD1-2 (n = 19) on duration of employment in the lead industry. Blood lead, zinc protoporphyrin, and plasma aminolevulinic acid concentrations, as well as ALAD genotype, duration of exposure, current tobacco use, and weight were examined as predictors or effect modifiers of levels of DMSA chelatable lead.

RESULTS

Blood lead concentrations ranged from 11 to 53 micrograms/dl, with a mean (SD) of 25.4 (10.2) micrograms/dl. After 5 mg/kg DMSA orally, the workers excreted a mean (SD) 85.4 (45.0) micrograms lead during a four hour urine collection (range 16.5-184.1 micrograms). After controlling for blood lead concentrations, duration of exposure, current tobacco use, and body weight, subjects with ALAD1-2 excreted, on average, 24 micrograms less lead during the four hour urine collection than did subjects with ALAD1-1 (P = 0.05). ALAD genotype seemed to modify the relation between plasma delta-aminolevulinic acid (ALA) and DMSA chelatable lead. Workers with ALAD1-2 excreted more lead, after being given DMSA, with increasing plasma ALA than did workers with ALAD1-1 (P value for interaction = 0.01).

CONCLUSIONS

DMSA chelatable lead may partly reflect the stores of bioavailable lead, and the current data indicate that subjects with ALAD1-2 have lower stores than those with ALAD1-1. These data provide further evidence that the ALAD genotype modifies the toxicokinetics of lead-for example, by differential binding of current lead stores or by differences in long-term retention and deposition of lead.

Links

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Authors+Show Affiliations

Schwartz BS
Department of Environmental Health Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, MD, USA.
Lee BK
No affiliation info available
Stewart W
No affiliation info available
Sithisarankul P
No affiliation info available
Strickland PT
No affiliation info available
Ahn KD
No affiliation info available
Kelsey K
No affiliation info available

MeSH

Administration, OralAdultBiomarkersChelating AgentsChromatography, High Pressure LiquidGenotypeHumansLeadMaleMiddle AgedOccupational ExposurePolymerase Chain ReactionPorphobilinogen SynthasePredictive Value of TestsRandom AllocationSuccimer

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

9166129

Citation

Schwartz, B S., et al. "Delta-Aminolevulinic Acid Dehydratase Genotype Modifies Four Hour Urinary Lead Excretion After Oral Administration of Dimercaptosuccinic Acid." Occupational and Environmental Medicine, vol. 54, no. 4, 1997, pp. 241-6.
Schwartz BS, Lee BK, Stewart W, et al. Delta-Aminolevulinic acid dehydratase genotype modifies four hour urinary lead excretion after oral administration of dimercaptosuccinic acid. Occup Environ Med. 1997;54(4):241-6.
Schwartz, B. S., Lee, B. K., Stewart, W., Sithisarankul, P., Strickland, P. T., Ahn, K. D., & Kelsey, K. (1997). Delta-Aminolevulinic acid dehydratase genotype modifies four hour urinary lead excretion after oral administration of dimercaptosuccinic acid. Occupational and Environmental Medicine, 54(4), 241-6.
Schwartz BS, et al. Delta-Aminolevulinic Acid Dehydratase Genotype Modifies Four Hour Urinary Lead Excretion After Oral Administration of Dimercaptosuccinic Acid. Occup Environ Med. 1997;54(4):241-6. PubMed PMID: 9166129.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - delta-Aminolevulinic acid dehydratase genotype modifies four hour urinary lead excretion after oral administration of dimercaptosuccinic acid. AU - Schwartz,B S, AU - Lee,B K, AU - Stewart,W, AU - Sithisarankul,P, AU - Strickland,P T, AU - Ahn,K D, AU - Kelsey,K, PY - 1997/4/1/pubmed PY - 1997/4/1/medline PY - 1997/4/1/entrez SP - 241 EP - 6 JF - Occupational and environmental medicine JO - Occup Environ Med VL - 54 IS - 4 N2 - OBJECTIVES: Previous research suggests that binding of lead by delta-aminolevulinic acid dehydratase (ALAD) may vary by ALAD genotype. This hypothesis was tested by examining whether ALAD genotype modifies urinary lead excretion (DMSA chelatable lead) after oral administration of dimercaptosuccinic acid (DMSA). METHODS: 57 South Korean lead battery manufacturing workers were given 5 mg/kg oral DMSA and urine was collected for four hours. Male workers were randomly selected from two ALAD genotype strata (ALAD1-1, ALAD1-2) from among all current workers in the two plants (n = 290). Subjects with ALAD1-1 (n = 38) were frequency matched with subjects with ALAD1-2 (n = 19) on duration of employment in the lead industry. Blood lead, zinc protoporphyrin, and plasma aminolevulinic acid concentrations, as well as ALAD genotype, duration of exposure, current tobacco use, and weight were examined as predictors or effect modifiers of levels of DMSA chelatable lead. RESULTS: Blood lead concentrations ranged from 11 to 53 micrograms/dl, with a mean (SD) of 25.4 (10.2) micrograms/dl. After 5 mg/kg DMSA orally, the workers excreted a mean (SD) 85.4 (45.0) micrograms lead during a four hour urine collection (range 16.5-184.1 micrograms). After controlling for blood lead concentrations, duration of exposure, current tobacco use, and body weight, subjects with ALAD1-2 excreted, on average, 24 micrograms less lead during the four hour urine collection than did subjects with ALAD1-1 (P = 0.05). ALAD genotype seemed to modify the relation between plasma delta-aminolevulinic acid (ALA) and DMSA chelatable lead. Workers with ALAD1-2 excreted more lead, after being given DMSA, with increasing plasma ALA than did workers with ALAD1-1 (P value for interaction = 0.01). CONCLUSIONS: DMSA chelatable lead may partly reflect the stores of bioavailable lead, and the current data indicate that subjects with ALAD1-2 have lower stores than those with ALAD1-1. These data provide further evidence that the ALAD genotype modifies the toxicokinetics of lead-for example, by differential binding of current lead stores or by differences in long-term retention and deposition of lead. SN - 1351-0711 UR - https://www.unboundmedicine.com/medline/citation/9166129/delta_Aminolevulinic_acid_dehydratase_genotype_modifies_four_hour_urinary_lead_excretion_after_oral_administration_of_dimercaptosuccinic_acid_ DB - PRIME DP - Unbound Medicine ER -