Cell proliferation in rat kidneys after prolonged treatment with lead.

Effects of chronic lead intoxication on cellular proliferation in rat kidneys were investigated by autoradiography. The rats were given intraperitoneal injections of lead acetate in aqueous solution for 6 months. At the end of this period, the proliferative activity of proximal tubular epithelial cells was about 15 times greater in rats given lead than in untreated controls. In the leaded rats approximately 40% of the proximal tubular cells contained intranuclear inclusions, approximately 0.5% of proximal tubular epithelial cells were labeled and approximately 6% of labeled cells contained intranuclear inclusions. Thus, cells with intranuclear inclusions can replicate DNA. Effects of chronic lead poisoning on the replication of proximal tubular cells in rats subjected to left uninephretomy before inception of treatment with lead were substantially the same. No renal carcinomas were found after 6 months of treatment with lead, but there was epithelial hyperplasia in some proximal tubules, with occasional atypia. The presence of increased synthesis of DNA and epithelial hyperplasia in the kidneys of rats chronically poisoned with lead suggests that the renal carcinogenicity of lead, observed by others, is related to lead-induced stimulation of renal cell proliferation.