The antitumor effect of oxygen radicals produced by hypoxanthine and x
anthine oxidase reaction was studied in an experimental rabbit model.
VX2 carcinomas were transplanted into rabbit hind legs. Hypoxanthine w
as administered continuously through the ear vein, while xanthine oxid
ase was administered simultaneously through the femoral artery. As a r
esult, hypoxanthine and xanthine oxidase reacted only in the hind leg,
and superoxide was produced in that area. The volume of the VX2 carci
noma was measured immediately prior to treatment and 7 days later. As
an index of lipid peroxidation, thiobarbituric acid-reactive substance
s in the tumor tissue were measured 60 min following infusion of hypox
anthine and xanthine oxidase. Tumor growth was suppressed significantl
y by the hypoxanthine-xanthine oxidase reaction, and thiobarbituric ac
id-reactive substances in the tumor tissue infused with hypoxanthine a
nd xanthine oxidase were significantly increased. In addition, the ant
itumor effect of the hypoxanthine and xanthine oxidase reaction was si
gnificantly inhibited by the administration of superoxide dismutase an
d catalase. Pathological examination showed that oxygen radicals produ
ced by hypoxanthine and xanthine oxidase reaction were selectively mor
e destructive for VX2 carcinoma tissue than muscle tissue surrounding
the tumor region. These results suggest that oxygen radicals produced
by hypoxanthine and xanthine oxidase reaction produce an anticancer ef
fect and that the VX2 carcinoma used in this study was more sensitive
to oxygen radicals than normal muscle tissue.