Nitric Oxide is an Important Mediator for Tumoricidal Activity In vivo

When cultured in vitro, peritoneal macrophages, obtained from mice previously inoculated with bacillus Calmette-Guérin, release nitric oxide, which is cytostatic and/or cytolytic for tumor cells. However, it is not known whether nitric oxide has antitumor effects in vivo. Here we demonstrate that ni...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1994-09, Vol.91 (20), p.9407-9411
Main Authors: Farias-Eisner, Robin, Sherman, Michael P., Aeberhard, Ernesto, Chaudhuri, Gautam
Format: Article
Language:English
Subjects:
Animals
Antibodies - pharmacology
Arginine - analogs & derivatives
Arginine - pharmacology
Cancer
Cell Line
Cell lines
Cell Survival - drug effects
Cell transplantation
Cytokines
Cytokines - pharmacology
Epithelial cells
Female
Humans
Immunity, Innate
Interferon-gamma - immunology
Interferon-gamma - pharmacology
Interferon-gamma - physiology
Lipopolysaccharides - pharmacology
Lymphocytes
Macrophages
Medical research
Mice
Mice, Inbred C3H
Mice, Nude
Mycobacterium bovis - immunology
Nitric Oxide - physiology
omega-N-Methylarginine
Ovarian Neoplasms - immunology
Ovarian Neoplasms - metabolism
Ovarian Neoplasms - pathology
Ovarian Neoplasms - therapy
Pharmacology
Reproductive system
Rodents
Teratocarcinoma
Tissue grafting
Transplantation, Heterologous
Tumor cell line
Tumor Cells, Cultured
Tumor Necrosis Factor-alpha - immunology
Tumor Necrosis Factor-alpha - pharmacology
Tumor Necrosis Factor-alpha - physiology
Tumors
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Summary:When cultured in vitro, peritoneal macrophages, obtained from mice previously inoculated with bacillus Calmette-Guérin, release nitric oxide, which is cytostatic and/or cytolytic for tumor cells. However, it is not known whether nitric oxide has antitumor effects in vivo. Here we demonstrate that nitric oxide is an important mediator of host resistance to syngeneic and xenogeneic ovarian tumor grafts in C3HeB/FeJ mice. A murine ovarian teratocarcinoma cell line, utilized to study the mechanism of bacillus Calmette-Guérin-induced host resistance to a syngeneic ovarian tumor, proliferated when transplanted intraperitoneally. Marked tumoricidal activity was observed, however, when these murine ovarian teratocarcinoma cells were transplanted 8 days after intraperitoneal bacillus Calmette-Guérin inoculation. In studies related to xenogeneic ovarian tumor grafts, tumoricidal activity was observed after intraperitoneal transplantation of a human epithelial ovarian cancer cell line, NIH:OVCAR-3. This cell line proliferates only in athymic nude (immunologically incompetent) mice. In both sets of experiments, tumoricidal activity was reduced by inhibition of nitric oxide synthesis. These results demonstrate the tumoricidal action of nitric oxide in vivo.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.91.20.9407