MANGANESE EFFECTS ON THE HUMAN NEUROBLASTOMA CELL-LINE SK-ER3

SK-ER3 cells were recently demonstrated to represent a valuable model for the study of estrogen-inducible differentiation of neural cells in culture. This system may constitute an important tool also for the an alysis of the effects of neurotoxic drugs. The present study demonstra tes that short term exposure to Mn causes increased proliferation rate of SK-ER3 cells regardless of their differentiation. Long term treatm ent causes cell death in undifferentiated cells at concentrations of t he metal as low as 100 nM. When the cells are differentiated with estr ogens, death is observed only with a Mn concentration two orders of ma gnitude higher. Measurement of neurite extension and quantitation of t yrosine hydroxylase content after long-term exposure to the metal allo w the conclusion that Mn does not alter the state of differentiation o f SK-ER3 cells induced by the treatment with the hormone. The study un derlines the importance of studying the effect of Mn in proliferating neural cells and demonstrates the toxic role of micromolar concentrati ons of the metal in fully differentiated neural cells. Since other aut hors produced evidence of effects of the metal on cell death and proli feration only at millimolar concentrations, and none described its pro liferative activity, the model utilized in the present study seems to be of particular interest. (C) 1996 Academic Press, Inc.