Nitric oxide (NO) has been emerged as an important intracellular and intercellular regulatory molecule having functions as diverse vasodilatation, neural coummunication, and host defense. In the immune system, NO produced by activated macrophage
or
neutrophil is known to kill tumor cells as a defense molecule. In addition, recent reports demonstrated that NO could interact with superoxide to generate peroxynitrite(ONOO), an anion and a potent oxidant, in macrophages or other cellular
systems.
The
production of peroxynitrite has been recognized to be associated with the activation and expression of inducible NO synthase (iNOS). In this study, to evaluate the role of NO and peroxynitrite in murine bladder tumor cells, the author investigate
the
effect of NO and peroxynitrite on the viability, cytotoxicity, and DNA fragmentation of MBT-2 cells.
@ES The results are as followings:
@EN 1. Activated macrophages treated with INS-γ, LPS, or INF-γ+LPS showed increment of nitrite(NO2) production and cytotoxicity against MBT-2 cells in a dose dependent manner. However, treatment with NGMMA, a NOS inhibitor, decreased NO2-
production
and cytotoxicity.
2. Treatment with SNP, a nitric oxide donor, increased NO2 production and DNA fragmentation (%), BUT DECREASED VIABILITY (%) of MBT-2 cells in a concentration dependent manner.
3. Treatment with peroxynitrite increased cytotoxicity and DNA fragmentation, but decreased viability of MBT-2 cells in a concentration dependent manner.
4. NO-and peroxynitrite-mediated increment of cytotoxicity in MBT-2 cells was corresponded to the programmed cell death, apoptosis.
Taken together, these data indicate that NO and peroxynitrite elaborated from macrophages or other cellular systems may increase the cytotoxicity of MBT-2 cells via the mechanism of apoptosis.
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