Differential effects of low-level lead exposure on the natural isozymes of erythrocyte 5′-nucleotidase

Objective: Erythrocyte pyrimidine 5′-nucleotidase (Pyr-5′-N) is highly sensitive to heavy metal inactivation in vitro and in vivo, and a number of studies have verified its usefulness as a biomarker of acute and chronic lead exposures. Retrospective and prospective studies attempted to determine whether the known linearity of Pyr-5′-N inhibition by lead concentrations above 40 μg/dL whole blood might continue into the lowest range of exposures now considered to be toxic in children (<10-20 μg/dL), thereby extending its value as a biomarker of lead exposure. Design: Activities of Pyr-5′-N and a lead-insensitive isozyme, deoxyribonucleotidase (d-5′-N), were compared to blood lead and free erythrocyte protoporphyrin (FEP) concentrations. Results: Pyr-5′-N activities in erythrocytes from 70 children displayed an inverse linear correlation with whole blood lead of 1-35 μg/dL, whereas d-5′-N did not correlate. There was no apparent minimum threshold for Pyr-5′-N inhibition by lead. Conclusions: Linearity of Pyr-5′-N inhibition by lead extends throughout the range of clinical concern in pediatric cases. Pyr-5′-N/d-5′-N activity ratios may provide an even more sensitive, internally controlled biomarker of low-level lead overburden, since both isozymes vary comparably in activity as a function of reticulocytosis and mean red cell age.