Quercetin and Dietary Lipids Alter the Cellular Redox Environment of the Colonocyte in the Promotion Stage of Colon Carcinogenesis.

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Title: Quercetin and Dietary Lipids Alter the Cellular Redox Environment of the Colonocyte in the Promotion Stage of Colon Carcinogenesis.
Author: Paulhill, Kimberly Jones
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 .
URI: http : / /hdl .handle .net /1969 .1 /ETD -TAMU -3027
Date: 2009-05-15

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Quercetin and Dietary Lipids Alter the Cellular Redox Environment of the Colonocyte in the Promotion Stage of Colon Carcinogenesis.. Available electronically from http : / /hdl .handle .net /1969 .1 /ETD -TAMU -3027 .

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