It was recently reported that vitamin C (500 mg/day for 6 weeks) administer
ed as a dietary supplement to healthy humans exhibits a prooxidant, as well
as an antioxidant effect in vivo. Here we show that high intakes of vitami
n C (500 mg/kg b.w. for 4 days) in the rat are able Ito markedly induce hep
atic cytochrome P4502E1-linked monooxygenases, measured as p-nitrophenol hy
droxylase activity and corroborated by means of Western blot analyses. Furt
hermore, using Electron Paramagnetic Resonance Spectroscopy (EPR) coupled t
o a spin-trapping technique, we have also found that this induction generat
es large amounts of the anion radical superoxide (O-2(.-)). Therefore we ca
n conclude that the adverse prooxidant outcomes (i.e. oxidative DNA damage)
associated to vitamin C supplementation, being associated to a typical rev
ersible boosting effect (i.e. enzymatic induction), may be easily controlle
d by a discontinuous supply. However, since the induced P4502E1 isoforms by
vitamin C are responsible for ethanol metabolism to highly reactive radica
ls, care should be taken even in moderate drinkers. (C) 1999 Elsevier Scien
ce Inc.