| dc.description.abstract | Quercetin (Q), a water-soluble flavonoid that is ubiquitous to foods of plant
origin is postulated to protect against colon cancer due to its antioxidant activity. In
contrast, we have shown that a dietary combination of fish oil (FO; n-3 fatty acids) and
pectin may protect against colon cancer by decreasing endogenous antioxidant enzyme
activities leading to increased reactive oxygen species (ROS), an inducer of apoptosis.
We hypothesized that adding an antioxidant to a FO diet may negate the beneficial
effects of FO by counteracting FO effects on colonocyte redox status. To test this, we
provided 40 rats with FO or CO (fiber = pectin) diets with Q being 0 or 0.45% of the diet
for 10 wk. All rats were injected with azoxymethane (AOM) on d 21 and 28.
Measurements included: aberrant crypt (AC) enumeration (colon cancer marker);
apoptosis (TUNEL assay); catalase (CAT), superoxide dismutase (SOD), and
glutathione peroxidase (GPx) activities; reduced and oxidized glutathione concentrations
(GSH/GSSG); and oxidative DNA damage (8-OHdG adducts). AC numbers were lower
in FO vs CO rats (p<0.0001), but tended to increase for FO diets containing Q
(P<0.098). The apoptotic index was higher (p<0.0001) when Q was added to the FO and
CO diets. Total SOD (lipid main effect, p=0.0136) and GPX activity (p=0.0025) was elevated in CO rats. CAT activity was higher (p=0.0204) in FO rats, however Q
diminished this effect. GSH was not affected by diet; yet, GSSG accumulated
(p=0.0554) in CO rats with Q as compared to CO rats without Q. The GSH/GSSG ratio
was lower (p=0.0314) in CO rats than in FO rats. There was no difference in 8-OHdG
adduct levels in FO vs CO rats, however, Q decreased 8-OHdG adducts in CO rats
(p=0.0428). Despite increasing apoptosis, Q did not significantly lower AC formation.
These data suggest that the distinct effects of the CO/Q and FO/Q combinations are
functioning through different mechanisms to induce apoptosis. The long-term
consequences of adding antioxidants such as Q to a diet thought to exert its anticancer
effect through a pro-oxidant mechanism are unknown and deserve further study. | en |
