Dose effects of flaxseed and its lignan on N-methyl-N-nitrosourea-induced mammary tumorigenesis in rats.
Dietary supplementation with flaxseed or its lignan secoisolariciresinol diglycoside (SDG) has reduced dimethylbenz[a]anthracene-induced mammary tumor size and number in rats. The objective of this study was to determine whether flaxseed has a dose-dependent effect on N-methyl-N-nitrosourea (MNU)-induced mammary tumor promotion and whether this effect can be attributed to its SDG. Two days after injection with MNU (50 mg/kg body wt i.p.), female Sprague-Dawley rats were fed a high-fat (20% soybean oil) AIN-93G basal diet alone (BD) or supplemented with flaxseed (2.5% F and 5% F) or SDG by gavage [SDG in 2.5% F (LSDG) and SDG in 5% F (HSDG)] for 22 weeks. Although tumors tended to be smallest in the 5% F group throughout the experimental period, flaxseed feeding did not significantly affect tumor size, multiplicity, or incidence in comparison to BD. However, there was a dose-dependent effect of SDG on tumor multiplicity. Tumor multiplicity was lowest in the HSDG group and highest in the LSDG group throughout treatment (p < 0.05), indicating that HSDG inhibited, whereas LSDG promoted, MNU-induced mammary tumor development. Tumor invasiveness and grade were decreased in all treatment groups compared with the BD (p < 0.032). Thus, although flaxseed feeding had no significant effect on tumor growth indexes, flaxseed and SDG treatment, regardless of dose, appeared to delay the progression of MNU-induced mammary tumorigenesis. Disparities between this study and previous studies on flaxseed may be related to differences in experimental design, the use and dose of a different carcinogen, and protective effects by the alpha-linolenic acid present in the BD.
Rickard
S E
SE
Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, ON, Canada.
Yuan
Y V
YV
Chen
J
J
Thompson
L U
LU
D000230:Adenocarcinoma / Q000178:diet therapy* / Q000473:pathology; D000818:Animals; D002072:Butylene Glycols / Q000627:therapeutic use*; D002273:Carcinogens; D004032:Diet; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D019597:Flax / Q000627:therapeutic use*; D005960:Glucosides / Q000627:therapeutic use*; D017705:Lignans / Q000627:therapeutic use; D008325:Mammary Neoplasms, Experimental / Q000178:diet therapy* / Q000473:pathology; D008770:Methylnitrosourea; D008517:Phytotherapy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D002072:Butylene Glycols; D002273:Carcinogens; D005960:Glucosides; D017705:Lignans; D008770:Methylnitrosourea; C090142:secoisolariciresinol diglucoside