This study describes the biological effects of hyperoxic treatment on BT4C rat
glioma xenografts in vivo with special reference to
tumor growth, angiogenesis, apoptosis, general morphology and gene expression parameters. One group of
tumor bearing animals was exposed to normobaric
hyperoxia (1 bar, pO(2) = 1.0) and another group was exposed to hyperbaric
hyperoxia (2 bar, pO(2) = 2.0), whereas animals housed under normal atmosphere (1 bar, pO(2) = 0.2) served as controls. All treatments were performed at day 1, 4 and 7 for 90 min. Treatment effects were determined by assessment of
tumor growth, vascular morphology (immunostaining for
von Willebrand factor), apoptosis by TUNEL staining and cell proliferation by Ki67 staining. Moreover, gene expression profiles were obtained and verified by real time quantitative PCR. Hyperoxic treatment caused a approximately 60% reduction in
tumor growth compared to the control group after 9 days (p < 0.01). Light microscopy showed that the
tumors exposed to
hyperoxia contained large "empty spaces" within the
tumor mass. Moreover,
hyperoxia induced a significant increase in the fraction of apoptotic cells ( approximately 21%), with no significant change in cell proliferation. After 2 bar treatment, the mean vascular density was reduced in the central parts of the
tumors compared to the control and 1 bar group. The vessel diameters were significantly reduced (11-24%) in both parts of the
tumor tissue. Evidence of induced cell death and reduced angiogenesis was reflected by gene expression analyses.Increased pO(2)-levels in experimental
gliomas, using normobaric and moderate
hyperbaric oxygen therapy, caused a significant reduction in
tumor growth. This process is characterized by enhanced cell death, reduced vascular density and changes in gene expression corresponding to these effects.