11 research outputs found
Effects of acute versus chronic hypoxia on DNA damage responses and genomic instability.
Questions exist concerning the effects of acute versus chronic hypoxic conditions on DNA replication and genomic stability that may influence tumorigenesis. Severe hypoxia causes replication arrest independent of S-phase checkpoint, DNA damage response, or transformation status. Arrests occur during both the initiation and elongation phases of DNA replication, correlated with a rapid decrease in available deoxynucleotide triphosphates. With fluctuating oxygen tensions in tumors, arrested hypoxic cells may undergo rapid reperfusion and reoxygenation that leads to reoxygenation-induced DNA damage. In cells subjected to chronic hypoxia, we found that replicative restart was inhibited along with numerous replication factors, including MCM6 and RPA, the latter of which limits the hypoxia-induced DNA damage response. In contrast, in cells where replicative restart occurred, it was accompanied by extensive reoxygenation-induced DNA damage and compromised DNA repair. We found that cells reoxygenated after acute hypoxia underwent rapid p53-dependent apoptosis. Our findings suggest that cells lacking functional p53 are more susceptible to genomic instability and potentially tumorigenesis if they experience reoxygenation after acute exposure to hypoxia
The First Hour of Extra-galactic Data of the Sloan Digital Sky Survey Spectroscopic Commissioning: The Coma Cluster
On 26 May 1999, one of the Sloan Digital Sky Survey (SDSS) fiber-fed
spectrographs saw astronomical first light. This was followed by the first
spectroscopic commissioning run during the dark period of June 1999. We present
here the first hour of extra-galactic spectroscopy taken during these early
commissioning stages: an observation of the Coma cluster of galaxies. Our data
samples the Southern part of this cluster, out to a radius of 1.5degrees and
thus fully covers the NGC 4839 group. We outline in this paper the main
characteristics of the SDSS spectroscopic systems and provide redshifts and
spectral classifications for 196 Coma galaxies, of which 45 redshifts are new.
For the 151 galaxies in common with the literature, we find excellent agreement
between our redshift determinations and the published values. As part of our
analysis, we have investigated four different spectral classification
algorithms: spectral line strengths, a principal component decomposition, a
wavelet analysis and the fitting of spectral synthesis models to the data. We
find that a significant fraction (25%) of our observed Coma galaxies show signs
of recent star-formation activity and that the velocity dispersion of these
active galaxies (emission-line and post-starburst galaxies) is 30% larger than
the absorption-line galaxies. We also find no active galaxies within the
central (projected) 200 h-1 Kpc of the cluster. The spatial distribution of our
Coma active galaxies is consistent with that found at higher redshift for the
CNOC1 cluster survey. Beyond the core region, the fraction of bright active
galaxies appears to rise slowly out to the virial radius and are randomly
distributed within the cluster with no apparent correlation with the potential
merger of the NGC 4839 group. [ABRIDGED]Comment: Accepted in AJ, 65 pages, 20 figures, 5 table
Mitochondrial inhibitor atovaquone increases tumor oxygenation and inhibits hypoxic gene expression in patients with non-small cell lung cancer
Clinical trial with omics and imaging data to study response to treatment