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-irradiation
damage
1 Department of Medical Oncology, City of Hope Medical Center, and 2 Department of Biology, City of Hope, Beckman Research Institute, Duarte, CA 91010
Gpx1 knockout (KO) mice had a higher number of regenerating
crypts in the jejunum than did Gpx2-KO or wild-type mice
analyzed 4 days after 
10 Gy 
-irradiation. Without -irradiation,
glutathione peroxidase (GPX) activity in the jejunal and ileal
epithelium of Gpx1-KO mice was <10 and ~35%,
respectively, of that of the wild-type mice. Four days after exposure
to 11 Gy, GPX activity in wild-type and Gpx1-KO ileum was
doubled and tripled, respectively. However, jejunal GPX activity was
not changed. Thus the lack of GPX activity in the jejunum is associated
with better regeneration of crypt epithelium after radiation.
Gpx2 gene expression was solely responsible for the increase
in GPX activity in the ileum, since radiation did not alter GPX
activity in Gpx2-KO mice. The intestinal Gpx2
mRNA levels of Gpx1-KO and wild-type mice increased up to
14- and 7-fold after radiation, respectively. Although the Gpx1-KO jejunum had higher levels of PGE2 than
the wild-type jejunum after exposure to 0 or 15 Gy, these differences
were not statistically significant. Thus whether GPX inhibits PG
biosynthesis in vivo remains to be established. We can conclude that
the Gpx2 gene compensates for the lack of Gpx1
gene expression in the ileal epithelium. This may have abolished the
protective effect in Gpx1-KO mice against the radiation
damage in the ileum.
Gpx2 gene induction; microcolony survival assay; Gpx2-knockout mice; antioxidant protein 2; gene compensation
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