The Influence of Flaxseed and Lignans on Colon Carcinogenesis and B-Glucuronidase Activity.
The Influence of Flaxseed and Lignans on Colon Carcinogenesis and B-Glucuronidase Activity.
Year: 1996
Authors: M Jenab, L U Thompson.
Publication Name: Carcinogenesis.
Publication Details: Volume 17; Number 6; 1343.
Abstract:
Short term studies by these authors have demonstrated that flaxseed and the mammalian precursor produced in flaxseed, SDG, reduce a number of risk parameters associated with mammary cancer. Since mammalian lignans are produced in the colon, they would be expected to produce their anti-carcinogenic effects principally at this site. Previous short term studies have shown that feeding flaxseed and flaxseed meal significantly reduced epithelial cell proliferation and the number of aberrant crypts (AC) and aberrant crypt foci (ACF), which are early markers of colon cancer risk. The effect of SDG on colon cancer has not been assessed. The present study was undertaken to ascertain 1) whether over the long term flaxseed exerts a colon cancer protective effect, 2) whether its effect may, in part, be due to its high content of SDG, 3) whether its effect is dose dependent at low levels of intake, and 4) whether any change in b-glucuronidase activity plays a role in the protective effect of flaxseed and SDG. b-glucuronidase is an inducible enzyme involved in the enterohepatic circulation and activation of carcinogens, mutagens and toxins and may be associated with an increased risk for colon cancer. Six groups of male rats were fed for 100 days either a basal high fat (20%) diet (BD), the BD supplemented with 2.5 or 5% flaxseed or 2.5 or 5% defatted flaxseed meal (equivalent to the respective flaxseed diets) or the BD with a daily gavage of 1.5 mg SDG. All rats were injected with a single dose of the carcinogen azoxymethane (15 mg/kg body weight) 1 week prior to commencing the dietary treatments. The results indicated that over the long term flaxseed and flaxseed meal can cause a significant reduction in AC multiplicity, suggesting a protective effect against colon cancer. SDG had an effect on AC formation similar to flaxseed and flaxseed meal, indicating that the protective effects of flaxseed appear to be due to SDG. Urinary lignan excretion, which is an indicator of mammalian lignan production, was significantly increased in the flaxseed and flaxseed meal groups. The total activity of cecal b-glucuronidase was significantly increased in a dose-dependent manner by the flaxseed and flaxseed meal diets. Compared with control animals, the number of aberrant crypts per foci was significantly reduced in the distal colon of the rats fed flaxseed, flaxseed meal or SDG. Four microadenomas and two polyps were observed in the control group, but not in the treated groups, indicating that the control group was progressing faster toward the onset of cancer. The total activity of b-glucuronidase was positively correlated with total urinary lignan excretion and negatively correlated with the total number of aberrant crypts and the total number of aberrant crypt foci in the distal colon. There were no significant differences between the flaxseed and the flaxseed meal groups in any measured parameter. The authors concluded that flaxseed feeding protects the colon from cancer, an effect due in part, to SDG. The results indicate that the protective effect of flaxseed and SDG appears to be associated with increased b-glucuronidase activity. However, increased b-glucuronidase activity has been linked to enhanced colon cancer risk. The authors present several theories as to why b-glucuronidase activity would increase with flaxseed and SDG feeding while at the same time significant anti-carcinogenic effects were observed. Other mechanisms of cancer protective action proposed included anti-oxidant effects, anti-mitotic and anti-proliferative effects of mammalian lignans.
