Hyperbaric oxygen inhibits benign and malignant human mammary epithelial cell proliferation.
BACKGROUND
Hyperbaric oxygenation (HBO) therapy is the administration of 100%-inhaled oxygen to patients at increased atmospheric pressure.


METHODS
We used an in vitro model to examine the effects of HBO on mammary cell proliferation. Normal mammary epithelia, primary tumor and metastatic tumor cells derived from the same patient and immortalized by transfection with the human papilloma virus E6 oncogene, as well as the MCF7 human mammary adenocarcinoma cell line, were studied.


RESULTS
HBO (97.9% O2, 2.1% CO2, 2.4 atmospheres absolute) inhibited the proliferation of all 4 cell types as measured by light microscopy, [3H]thymidine uptake, a tetrazolium-based colorimetric assay and a clonogenicity assay. The anti-proliferative effect of HBO was time-dependent (p < 0.01 for all 4 cell types). Hyperoxia alone (95% O2, 5% CO2, 1 atmosphere absolute) and increased atmospheric pressure alone (8.75% O2, 2.1% CO2, 2.4 atmospheres absolute) also inhibited proliferation, but their effects were not as profound as HBO (p < 0.01 when either hyperoxia or increased pressure was compared to HBO for all 4 cell types). HBO enhanced the anti-proliferative effects of melphalan (p < 0.05), gemcitabine (p < 0.001) and paclitaxel (p < 0.001). The clonogenicity assay demonstrated that the effects of HBO were still evident 2 weeks after the exposure (p < 0.01 for all 4 cell types). Experiments using Hoechst-propidium iodide or annexin V-propidium iodide staining showed no HBO-induced increases in necrosis or apoptosis.


CONCLUSIONS
HBO inhibits benign and malignant mammary epithelial cell proliferation, but does not enhance cell death.
Granowitz
Eric V
EV
Department of Medicine, Baystate Medical Center, Tufts University School of Medicine, Springfield, MA 01199, USA. eric.granowitz@bhs.org
Tonomura
Noriko
N
Benson
Rita M
RM
Katz
Deborah M
DM
Band
Vimla
V
Makari-Judson
Grace P
GP
Osborne
Barbara A
BA
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology* / Q000821:virology; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology* / Q000821:virology; D048708:Cell Growth Processes / Q000187:drug effects; D002472:Cell Transformation, Viral; D004357:Drug Synergism; D052163:Human papillomavirus 6 / Q000235:genetics; D006801:Humans; D006931:Hyperbaric Oxygenation; D042361:Mammary Glands, Human / Q000166:cytology / Q000187:drug effects*; D009857:Oncogenes; D010100:Oxygen / Q000008:administration & dosage / Q000494:pharmacology*; D014162:Transfection
D010100:Oxygen