Thallium induces apoptosis in rat pheochromocytoma (PC12) cells.

HANZEL, C. E.; VERSTRAETEN, S. V.

Pinamar, Buenos Aires, Argentina

Congreso; XLI Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular, X Congreso Panamerican Association for Biochemistry and Molecular Biology y XX Reunión Anual Sociedad Argentina de Neuroquímica; 2005

Thallium (Tl) is a non-essential heavy metal, with two oxidation states (Tl+ and Tl3+). Tl+ causes mitochondrial swelling, neurodegeneration, and an increase in lipid oxidation products content. Working with PC12 cells, we investigated the cytotoxic effects of Tl+ and Tl3+ (10-250 μM) (1-72 hs). The number of viable cells, assesed by the incorporation of the probes calcein AM and ethidium homodimer and the reduction of MTT, decreased in Tl-containing samples in a concentration-and time-dependent manner. GSH content decreased at 24 hours of incubation in the presence of the metal as evaluated by the incorporation of the probe mBCI. Mitochondrial membrane potential decreased, as evaluated by the uptake of the fluorescent probe rhodamine 123, effect that was accompanied by an increase in H2O2 content, measured by the oxidation of the probe dihydrorhodamine 123. An increase in the number of apoptotic cells was found when the nuclear morphology was assesed using the probes acridine orange and ethidium bromide. Western blot analysis showed a higher PARP cleavage. In summary, Tl causes a decrease in GSH, alters mitochondrial functionality increasing H2O2 content, molecule that could trigger cell apoptosis.