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Kyu-Yoon Hwang,^1,2 Byung-Kook Lee,^1,2 Joseph P. Bressler,^3,4 Karen I. Bolla,^1,3 Walter F. Stewart,^1,5 and Brian S. Schwartz^5,6

¹Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA; ²Department of Preventive Medicine, School of Medicine, Soonchunhyang University, Chunan, Republic of Korea; ³Department of Neurology, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA; ⁴Division of Toxicological Sciences, Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA; ⁵Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USA; ⁶Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA

Abstract

At picomolar concentrations, lead activates protein kinase C (PKC) . This activation has been implicated in the neurotoxicity of lead. No prior study has evaluated the association of PKC activity with neurobehavioral function in humans. The purpose of this study was to determine whether PKC activity is associated with neurobehavioral function or modifies the relationship between blood lead levels and neurobehavioral test scores. In this cross-sectional study of 212 current lead workers in the Republic of Korea, we assessed blood lead levels, neurobehavioral test scores, and PKC activity. PKC activity was determined by measuring the levels of phosphorylation of three erythrocyte membrane proteins (spectrin and the 52-kDa and 48-kDa subunits of band 4.9) , using an in vitro back-phosphorylation assay. When linear regression was used to control for confounding variables, blood lead was a significant predictor of decrements in performance on tests of psychomotor function, manual dexterity, and executive ability. In linear regression models, back-phosphorylation levels were not associated with neurobehavioral test scores, but when dichotomized at the median, back-phosphorylation levels modified the relationship between blood lead and test scores. For spectrin and the 52-kDa and 48-kDa subunits of band 4.9, 5, 2, and 5 of 14 interaction terms, respectively, had associated p-values < 0.10, all with positive signs, indicating that blood lead was associated with worse test scores only in subjects with lower back-phosphorylation levels. These data indicate that blood lead levels are associated with decrements in neurobehavioral test scores, mainly in the domains of manual dexterity and psychomotor function, but only in subjects with lower in vitro back-phosphorylation levels, which is equivalent to higher in vivo PKC activity. We hypothesize that subjects with higher PKC activity in the presence of lead may be more susceptible to the health effects of lead. Key words: back-phosphorylation, blood lead, neurobehavioral function, protein kinase C, susceptibility. Environ Health Perspect 110:133-138 (2002) . [Online 10 January 2002]

http://ehpnet1.niehs.nih.gov/docs/2002/110p133-138hwang/ abstract.html

Address correspondence to B.S. Schwartz, Division of Occupational and Environmental Health, Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University, Room 7041, 615 North Wolfe Street, Baltimore, MD 21205 USA. Telephone: (410) 955-4130. Fax: (410) 955-1811. E-mail: bschwart@jhsph.edu

This research was supported by grants ES01798 (B.S. Schwartz) , ES07980 (J.P. Bressler) , and ES08785 (J.P. Bressler) .

Received 23 May 2001 ; accepted 31 July 2001.