The influence of flaxseed and lignans on colon carcinogenesis and beta-glucuronidase activity.
Flaxseed, the richest source of mammalian lignan precursors, such as secoisolariciresinol diglycoside (SD), has been shown over the short term to decrease some early markers of colon cancer risk. This study determined whether over the long term flaxseed still exerts a colon cancer protective effect, whether its effect may, in part, be due to its high content of SD and whether any change in beta-glucuronidase activity plays a role in the protective effect. Six groups of male Sprague-Dawley rats were fed for 100 days either a basal high fat (20%) diet (BD), BD supplemented with 2.5 or 5% flaxseed or 2.5 or 5% defatted flaxseed (equivalent to the respective flaxseed diets) or BD with a daily gavage of 1.5 mg SD. All rats were injected with a single dose of azoxymethane (15 mg/kg body wt) 1 week prior to commencing the dietary treatments. Urinary lignan excretion, which is an indicator of mammalian lignan production, was significantly increased in the flaxseed and defatted flaxseed groups. The total activity of cecal beta-glucuronidase was significantly increased in a dose-dependent manner by the flaxseed and defatted flaxseed diet groups. Compared with the control the number of aberrant crypts per focus was significantly reduced in the distal colon of the treated rats. Four microadenomas and two polyps were observed in the control group, but not in the treated groups. The total activity of beta-glucuronidase was positively correlated with total urinary lignan excretion and negatively 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 corresponding defatted flaxseed groups. It is concluded that flaxseed has a colon cancer protective effect, that it is due, in part, to SD and that the protective effect of flaxseed is associated with increased beta-glucuronidase activity.
Jenab
M
M
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Ontario, Canada.
Thompson
L U
LU
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects; D002072:Butylene Glycols / Q000627:therapeutic use* / Q000633:toxicity / Q000652:urine; D002432:Cecum / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000517:prevention & control*; D004435:Eating / Q000187:drug effects; D005227:Fatty Acids / Q000096:biosynthesis; D005960:Glucosides / Q000627:therapeutic use* / Q000633:toxicity / Q000652:urine; D005966:Glucuronidase / Q000187:drug effects / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D017705:Lignans / Q000627:therapeutic use* / Q000633:toxicity / Q000652:urine; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010936:Plant Extracts / Q000627:therapeutic use* / Q000633:toxicity; D011230:Precancerous Conditions / Q000201:enzymology / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D012639:Seeds
D016588:Anticarcinogenic Agents; D002072:Butylene Glycols; D005227:Fatty Acids; D005960:Glucosides; D017705:Lignans; D010936:Plant Extracts; D005966:Glucuronidase; C090142:secoisolariciresinol diglucoside