Lead-induced inclusion bodies: results of ethylenediaminetetraacetic acid treatment

Earlier studies have shown that lead-induced nuclear inclusion bodies are composed of a lead-protein complex. Twenty-four hours after treatment of a lead-poisoned rat with a single dose of ethylenediaminetetraacetic acid (EDTA), urinary excretion of lead is maximally increased and the lead content of the kidneys is significantly decreased. Inclusion bodies in renal cell nuclei at this time are found in various stages of dissolution and migration out of the nucleus. The outer fibrillary margin becomes loosened, and slight disruption occurs at the periphery of the inclusion. Some inclusion bodies appear to be moving through the nuclear membrane. There is an invagination of both inner and outer nuclear membranes. Numerous cytoplasmic vacuoles occur which contain fibrillar material resembling portions of intact nuclear inclusions. Kidney nuclei of rats 24 hours after three daily injections of EDTA have no inclusion bodies. Whether the nuclear-cytoplasmic exchange occurs by dilation of a nuclear pore or by another mode of separation of nuclear membranes cannot be determined. This experiment demonstrates that nuclear inclusion bodies formed in lead poisoning are disrupted and removed from the nuclei by the administration of EDTA. This change corresponds with peak urinary excretion of lead. The sharp increase in urinary lead following EDTA therapy must reflect, at least in part, chelation and excretion of sequestered lead bound to nuclear protein.