Carcinogenesis, Vol 18, 2373-2377, Copyright © 1997 by Oxford University Press
S Cadenas, G Barja, HE Poulsen and S Loft
Dietary antioxidants may influence cancer risk and aging by modifying
oxidative damage. The effect of graded dietary doses of the antioxidant
vitamins C and E on oxidative DNA damage was studied in the liver of
guinea-pigs under normal conditions. Like human beings, guinea-pigs cannot
synthesize ascorbate and alpha-tocopherol. In one experiment, three groups
of 6-8 guinea-pigs were fed diets containing 15 mg of vitamin E/kg chow and
three different amounts of vitamin C (33,660 or 13,200 mg/kg) for 5 weeks.
In a second experiment, three groups of seven guinea-pigs were fed diets
containing 660 mg of vitamin C/kg and three different amounts of vitamin E
(15, 150 or 1500 mg/kg) for 5 weeks. The three graded levels of each
vitamin respectively represent marginal deficiency, an optimum
supplementation and a megadose. Oxidative damage to liver DNA was estimated
by measuring 8-oxo-7,8- dihydro-2'-deoxyguanosine (oxo8dG) referred to
deoxyguanosine (dG) by means of high-performance liquid chromatography with
simultaneous electrochemical-coulometric and ultraviolet detection. The
level of ascorbate in the liver was 0.034 +/- 0.051, 1.63 +/- 1.06 and 1.99
+/- 0.44 micromol/g in the low, medium and high dose ascorbate groups (59-
fold variation). The liver concentration of alpha-tocopherol was 28 +/- 11,
63 +/- 18 and 187 +/- 34 nmol/g in the low, medium and high dose
alpha-tocopherol groups (7-fold variation). The level of oxo8dG in the
liver DNA was 1.89 +/- 0.32, 1.94 +/- 0.78 and 1.93 +/- 0.65 per 10(5) dG
in the low, medium and high dose ascorbate groups (no effect: P > 0.05).
In the low, medium and high dose alpha-tocopherol groups oxo8dG level in
the liver DNA was 2.85 +/- 0.70, 2.74 +/- 0.66 and 2.61 +/- 0.92 per 10(5)
dG (no effect: P > 0.05). It is concluded that even very large
variations in the content of the antioxidant vitamins C and E in the diet
and liver have no influence on the steady-state level of oxidative damage
to guanine in the liver DNA of normal unstressed guinea-pigs.
ARTICLES
Oxidative DNA damage estimated by oxo8dG in the liver of guinea-pigs supplemented with graded dietary doses of ascorbic acid and alpha- tocopherol
Department of Pharmacology, Panum Institute, University of Copenhagen, Copenhagen N, Denmark.
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