A role of red cell pyrimidine 5?-nucleotidase in experimental lead poisoning

Abstract

Intravenous administration of lead acetate to rabbits for 10 weeks at 2 week intervals resulted in significantly elevated blood lead levels, slight anemia with marked microspherocytosis and moderate basophilic stippling, and marked depression of red cell delta-aminolevulinic acid (ALA) dehydratase activity. However the decrease in red cell pyrimidine 5'-nucleotidase (P5N) activity was slight when compared to the red cell P5N activity of comparable reticulocyte-rich blood, and intracellular accumulation of pyrimidine nucleotides could not be demonstrated. In the in vitro inhibition test the same degree of inhibition of red cell P5N activity seen in hereditary red cell P5N deficiency was obtained by using a lead concentration 200--400 times higher than the lead levels detected in human plumbism. Most importantly, there were no differences in the lead-induced inhibition of human and rabbit red cell P5N. From the results of the in vitro inhibition test, lead-induced red cell P5N deficiency appears to be one of several pathogenic mechanisms in chronic lead exposure associated with the accumulation of lead in bone marrow. A decrease in rec cell P5N activity could not be demonstrated despite the marked depression in red cell ALA dehydratase activity, and slight anemia with marked microspherocytosis and moderate basophilic stippling in this experiment. These results suggest that lead affects red cells at multiple metabolic loci.