In vitro aberrant gene expression as the indicator of lead-induced neurotoxicity in U-373MG cells

Lead is an important neurobehavioral toxicant and may interfere with developmental processes in the brain resulting in impairment of its functions. U-373MG, a human glioma cell line, was cultured in Dulbecco's modified Eagles' medium supplemented with either 20 or 10% FBS (fetal bovine serum) to explore the possible indications for lead-induced toxicity. Although lead did not affect cell growth rate in concentrations ranging from 0.01 to 10 μM, it substantially altered gene expression analyzed by reverse- transcription polymerase chain reaction. With 10% FBS culture, lead affected the gene expression in a dose-dependent relationship. It enhanced the expression of tumor necrosis factor-α (TNF-α), but decreased those of interleukin-1β (IL-1β), interleukin-6 (IL-6), γ-aminobutyric acid (GABA) transaminase, and glutamine synthetase. With 20% FBS culture, lead also profoundly increased TNF-α and IL-1β; however, it did not extensively affect the other genes examined above. Thus, the highly sensitive changes of gene expression of these cytokines or metabolic enzymes after treatments with lead acetate evidenced their usefulness as indicators for in vitro measurement of lead-induced neurotoxicity. (C) 2000 Elsevier Science Ireland Ltd.