1. Biometals. 2010 Mar 8. [Epub ahead of print]

Tellurite-induced oxidative stress leads to cell death of murine hepatocarcinoma 
cells.

Sandoval JM, Levêque P, Gallez B, Vásquez CC, Buc Calderon P.

Laboratorio de Microbiología Molecular, Facultad de Química y Biología,
Universidad de Santiago de Chile, Santiago, Chile.

Data regarding tellurium (Te) toxicity are scarce. Studies on its metabolism,
performed mainly in bacteria, underline a major role of reactive oxygen species
(ROS). We investigated whether tellurite undergoes redox cycling leading to ROS
formation and cancer cell death. The murine hepatocarcinoma Transplantable Liver 
Tumor (TLT) cells were challenged with tellurite either in the presence or in the
absence of different compounds as N-acetylcysteine (NAC), 3-methyladenine,
BAPTA-AM, and catalase. NAC inhibition of tellurite-mediated toxicity suggested a
major role of oxidative stress. Tellurite also decreased both glutathione (GSH)
and ATP content by 57 and 80%, respectively. In the presence of NAC however, the 
levels of such markers were almost fully restored. Tellurite-mediated ROS
generation was assessed both by using the fluorescent, oxidation-sensitive probe 
dichlorodihydrofluorescein diacetate (DCHF-DA) and electron spin resonance (ESR) 
spectroscopy to detect hydroxyl radical formation. Cell death occurs by a
caspase-independent mechanism, as shown by the lack of caspase-3 activity and no 
cleavage of poly(ADP-ribose)polymerase (PARP). The presence of gamma-H2AX
suggests tellurite-induced DNA strand breaking, NAC being unable to counteract
it. Although the calcium chelator BAPTA-AM did show no effect, the rapid
phosphorylation of eIF2alpha suggests that, in addition to oxidative stress, an
endoplasmic reticulum (ER) stress may be involved in the mechanisms leading to
cell death by tellurite.

PMID: 20213267 [PubMed - as supplied by publisher]