Effects of Maternal Exposure to Cow's Milk High or Low in Isoflavones on Carcinogen-Induced Mammary Tumorigenesis among Rat Offspring

Abstract

We investigated whether maternal exposure during pregnancy to cow's milk containing endogenous estrogens and insulin-like growth factor 1 (IGF-1) and either high or low levels of isoflavones from dietary legumes (HIM and LIM, respectively) affected carcinogen-induced mammary carcinogenesis in female rat offspring. Pregnant Sprague-Dawley rats were given HIM, LIM, or tap water (control) from gestational day (GD) 11 until birth; hereafter all rats received tap water. Mammary tumorigenesis was induced by administrating 7,12-dimethylbenz[a]anthracene (DMBA) on postnatal day 50. No differences in maternal serum estradiol (P ¼ 0.19) and IGF-1 levels (P ¼ 0.15) at GD 19 or birth weight among the milk and water groups were seen, but estradiol, and IGF-1 levels and birth weight were numerically higher in the LIM group than in the HIM group. Puberty onset occurred earlier in the LIM offspring than in controls (P ¼ 0.03). Although the high isoflavone content seemed to prevent the effect on circulating estradiol and IGF-1 levels and advanced puberty onset seen in the LIM group, HIM increased DMBA-DNA adducts in the mammary gland and tended to increase mammary tumorigenesis. In contrast, offspring exposed to LIM in utero, did not exhibit increased breast cancer risk, despite having higher estradiol and IGF-1 environment and consequently earlier puberty onset. These results indicate that the phytochemical content in the cow's milk, consumed by a pregnant dam, determines how milk affects the offspring. Cancer Prev Res; 4(5); 694-701. Ó2011 AACR.

Maternal Obesity and Developmental Programming of Metabolic Disorders in Offspring: Evidence from Animal Models

“…However, interpretation of specific macronutrient effects is very difficult due to the widely varied macronutrient sources across the added foods and the dietary interaction across the varied fat, protein, and carbohydrate backgrounds. Further, there is some evidence that specific components utilised in the cafeteria diet may have deleterious effects such as those related to dairy intake in the rodent [34, 35] and oxidative stress [36]. Recent work by Sampey et al investigated the obesogenic and inflammatory consequences of a cafeteria diet compared to a lard-based 45% (of calories) HF diet in the rodent.…”

Analytical methods used to quantify isoflavones in cow’s milk: a review

“…hydrolysis (0.2 mL sulfatase/glucuronidase from H. pomatia , 52 °C, and 2 h) - Centrifugation - SPE (C18) - Evaporation to dryness - Reconstitution in MeOH (80%, v / v ) - Filtration (0.45 μm) Flachowsky et al ( 2011 ) BA, DA, EQ, FO, and GL ( feeding experiments and health impact experiments ) Frozen (−20 °C) - Equilibration at room temperature - Enz. hydrolysis (β-glucuronidase, 100 μL.4 mL −1 of milk, 37 °C, and 1 h) - Centrifugation (cream and precipitate were discarded) - Double L/L extraction (hexane and ethyl acetate, 3 × 3 mL) - Evaporation to dryness - Re-suspension (0.5 mL acetonitrile) - Filtration (0.2 μm) Nielsen et al ( 2011 ), Skaanild and Nielsen ( 2010 ), Nielsen et al ( 2009 ) and Andersen et al ( 2009b ) DA, EQ, GE, and GL ( technological processing and feeding experiments ) Frozen (−20 °C) - Enz. hydrolysis (100 μL β-glucuronidase [11,400 U.mL −1 ]/ sulfatase [3200 U.mL −1 ] from H. pomatia type H2 were added at 2 mL of milk and 3 mL of acetate buffer [0.1 M and pH 5], 37 °C, and 12 h) - L/L extraction (3 × 2 mL ethylacetate) - Centrifugation - Evaporation to dryness - Reconstitution (0.5 mL methanol:water [1:1, v / v ]) Křížová et al ( 2011a ), Křížová et al ( 2011b ), Krajčová et al ( 2010 ), and Třináctý et al ( 2009 ) BA, DA, EQ, FO, GE, and GL ( commercial milks ) N.C. - L/L extraction (10 mL milk/10 mL acetone/acetate buffer [2 M, pH 5.2, 9:1, v / v ]) - Enz.…”

Proliferative effect of whey from cows’ milk varying in phyto-oestrogens in human breast and prostate cancer cells

“…The total levels of phyto-oestrogens that can be achieved in cows' milk through specific feeding practices are relatively low compared with the 200-6500 mg/l that can be measured in soy milk and other soy-based beverages (Kano et al 2006;Dip et al 2008). However, the relatively low concentrations of phyto-oestrogens in milk do not rule out any biological effects of milk phyto-oestrogens, as previous in-vitro and in-vivo studies have already shown (Nielsen et al 2009(Nielsen et al , 2011. Owing to the large differences in milk phyto-oestrogen content following the B1 feeding and the two red clover silage based diets (R1 and R2) in the present study, we hypothesized that there would be differences in the proliferative activity of whey in the assays applied.…”