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Toxicological Sciences 62, 280-288 (2001)
Copyright © 2001 by the Society of Toxicology


NEUROTOXICOLOGY

Associations of Lead Exposure and Dose Measures with Erythrocyte Protein Kinase C Activity in 212 Current Korean Lead Workers

Kyu-Yoon Hwang*,{dagger}, Brian S. Schwartz*,{ddagger},§, Byung-Kook Lee*,{dagger}, Paul T. Strickland*, Andy C. Todd and Joseph P. Bressler*,||,,1

* Department of Environmental Health Sciences, School of Hygiene and Public Health, The Johns Hopkins University, Baltimore, Maryland; {dagger} Department of Preventive Medicine, School of Medicine, Soonchunhyang University, Chunan, Republic of Korea; {ddagger} Department of Epidemiology, School of Hygiene and Public Health, The Johns Hopkins University, Baltimore, Maryland; § Department of Medicine, School of Medicine, The Johns Hopkins University, Baltimore, Maryland; Department of Community Medicine and Preventive Medicine, Mount Sinai Medical Center, New York, New York; and Departments of || Neurology, School of Medicine and Neurotoxicology, Kennedy Krieger Institute, The Johns Hopkins University, Baltimore, Maryland

Lead can replace calcium in enzyme assays that measure protein kinase C activity and lead activates protein kinase C in human erythrocytes after exposure to lead in vitro. To examine the relevance of these observations to lead exposure in humans, we studied the associations of lead found in blood or tibia with activation of protein kinase C in erythrocytes isolated from workers in the lead industry. We examined erythrocytes among 212 lead workers, with a mean (±SD) age of 39.1 (10.0) years and exposure duration of 8.1 (6.5) years and measured protein kinase C activation by an in vitro back-phosphorylation assay. After adjustment for potential confounding factors (age and sex), tibia lead and exposure duration were significantly associated with erythrocyte protein kinase C activation (both p values < 0.05). No associations were observed between protein kinase C activation and blood-lead or zinc-protoporphyrin levels. These findings suggest that human exposure to lead results in activation of erythrocyte protein kinase C, which may be directly relevant to the neurotoxicity of lead.

Key Words: blood lead; tibia lead; protein kinase C; back-phosphorylation.


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