Sammendrag
There is little in vitro data available on long-term effects of TiO2 exposure. Such data are
important for improving the understanding of underlying mechanisms of adverse health effects of
TiO2
. Here, we exposed pulmonary epithelial cells to two doses (0.96 and 1.92 µg/cm2
) of TiO2
for
13 weeks and effects on cell cycle and cell death mechanisms, i.e., apoptosis and autophagy were
determined after 4, 8 and 13 weeks of exposure. Changes in telomere length, cellular protein levels
and lipid classes were also analyzed at 13 weeks of exposure. We observed that the TiO2 exposure
increased the fraction of cells in G1-phase and reduced the fraction of cells in G2-phase, which was
accompanied by an increase in the fraction of late apoptotic/necrotic cells. This corresponded with
an induced expression of key apoptotic proteins i.e., BAD and BAX, and an accumulation of several
lipid classes involved in cellular stress and apoptosis. These findings were further supported by
quantitative proteome profiling data showing an increase in proteins involved in cell stress and
genomic maintenance pathways following TiO2 exposure. Altogether, we suggest that cell stress
response and cell death pathways may be important molecular events in long-term health effects
of TiO2
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