Effects of thallium on PC12 cells proliferation. Modulation by EGF

PINO, M. T. L.; VERSTRAETEN, S. V.

San Miguel de Tucuman, Tucuman

Congreso; XLV Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2009

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

The mechanisms involved in the cytotoxicity of the heavy metal thallium (Tl) are still under elucidation. We previously demonstrated that Tl(I) and Tl(III) alter PC12 cells redox state and cause apoptosis. In the present work we investigated whether Tl(I) and/or Tl(III) (1-100 M) could affect PC12 cells proliferation either in the absence or presence of epidermal growth factor (EGF). After 24 h, Tl(I) caused the accumulation of cells in S phase while Tl(III)-treated samples had higher percentage of cells in G2/M phase. Both Tl(I) and Tl(III) increased the number of apoptotic cells. These effects were partially prevented by EGF only in Tl(III)-treated cells. Tl(III) but not Tl(I) increased PC12 cells plasma membrane fluidity at the water-lipid interface, without affecting lipids hydration or the fluidity of the hydrophobic portion of the bilayer. Again, EGF protected cells from Tl(III) effects. Cells pre-loading with Tl had no effect on PC12 cells cycle, either in the absence or in the presence of EGF. Together, present results indicate that in addition to promoting cell apoptosis, Tl alters cell cycle and membrane properties. The observation that EGF could modulate Tl(III)- but not Tl(I)-mediated effects suggests different mechanisms could be operative in the cytotoxic effects of both cations. Supported by grants of UBA (B086), ANPCyT (PICT 32273) and CONICET (PIP 112-200801-01977).