Thallium exposure leads to cell death through the induction of apoptosis.

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

Rosario, Santa Fe, Argentina

Congreso; XLII Reunión Anual de la Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2006

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

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+ (10-100 μM) (24 hs). Previous results showed that both Tl+ and Tl3+ decrease mitochondrial membrane potential, effect that was accompanied by an increase in H2O2 content. A significant decrease in GSH content was also observed. To study the possible mechanisms of cell death involved in Tl toxicity nuclear morphology was characterized using the probes acridine orange and ethidium bromide. An increase in the number of apoptotic cells was found. Western blot analysis showed higher PARP cleavage, the release of cytochrome c into the cytosol, and a diminished bcl-2 content. Besides, an increase in caspase 8 activity was observed when the cells were incubated in the presence of Tl3+. Neither autophagic cell death as evaluated by the incorporation of the probe MDC into autophagic vacuoles, nor necrosis as evaluated by LDH activity, were involved in Tl toxicity. In summary, Tl caused a decrease in GSH, and altered mitochondrial functionality increasing H2O2 content, effect/s that could trigger cell apoptosis.