1: Int J Cancer.  2004 May 1;109(5):768-73.  

Nitric oxide as a radiosensitizer: Evidence for an intrinsic role in addition to
its effect on oxygen delivery and consumption.

Jordan BF, Sonveaux P, Feron O, Gregoire V, Beghein N, Dessy C, Gallez B.

Laboratory of Medicinal Chemistry and Radiopharmacy, Universite Catholique de
Louvain, Avenue Mounier 73, Brussels, Belgium.

Different nitric oxide (NO)-mediated treatments (e.g., isosorbide dinitrate,
insulin and electrical stimulation of the host tissue) have been investigated
for their effects on tumor oxygenation and radiation sensitivity. We further
address the issue of the role played by modulation of the NO-pathway in tumor
radiosensitivity. For this purpose, the local concentration of NO was monitored
after treatment in FSaII tumors and a comparison between the sensitivity of LLC
tumors implanted both on eNOS(-/-) and wild-type (WT) mice was carried out.
First, we demonstrate the central role played by eNOS in the radiosensitizing
effect after application of insulin treatment and electrical stimulation: a
significant increase in tumor NO content is induced by these treatments and the
increase in tumor oxygenation, as well as the radiosensitizing effect are
abolished in eNOS knock-out mice, in contrast to WT mice. Second, by comparing
the level of oxygen and NO achieved in tumors after NO-mediated treatments and
carbogen, we provide evidence that these NO-mediated treatments are not simply
acting by a single oxygen effect. These treatments induced significant regrowth
delays compared to carbogen, despite a smaller increase in tumor oxygenation.
For the NO-mediated treatments, there was a direct correlation between the NO
content and the radiosensitizing effect. These data strongly suggest that NO is
a complementary factor additive to oxygen in determining the sensitivity to
irradiation and we therefore propose that NO acts as an intrinsic
radiosensitizer in vivo. Copyright 2004 Wiley-Liss, Inc.

PMID: 14999787 [PubMed - in process]