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 develo pmental 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 exp lore the possible indications for lead-induced toxicity. Although lead did not affect cell growth rate in concentrations ranging from 0.01 to 10 mu M, it substantially altered gene expression analyzed by reverse-transcription polymerase chain reaction. With 10% FBS culture, lead affected the gene ex pression in a dose-dependent relationship. It enhanced the expression of tu mor necrosis factor-alpha (TNF-alpha), but decreased those of interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), gamma-aminobutyric acid (GABA) tra nsaminase, and glutamine synrhetase. With 20% FBS culture: lead also profou ndly increased TNF-alpha and IL-1 beta; however, it did not extensively aff ect the other genes examined above. Thus. the highly sensitive changes of g ene expression of these cytokines or metabolic enzymes after treatments wit h lead acetate evidenced their usefulness as indicators for in vitro measur ement of lead-induced neurotoxicity. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.