Feeding of soy protein isolate to rats during pregnancy and lactation suppresses formation of aberrant crypt foci in their progeny's colons: interaction of diet with fetal alcohol exposure

Abstract

Soy protein isolate (SPI) in the diet may inhibit colon tumorigenesis. We examined azoxymethane (AOM)-induced aberrant crypt foci (ACF) in male rats in relation to lifetime, pre-weaning, or post-weaning dietary exposure to SPI and also within the context of fetal alcohol exposure. Pregnant Sprague Dawley rats were fed AIN-93G diets containing casein (20%, the control diet) or SPI (20%) as the sole protein source starting on gestation day 4 (GD 4). Progeny were weaned on postnatal day (PND) 21 to the same diet as their dams and were fed this diet until termination of the experiment at PND 138. Rats received AOM on PND 89 and 96. Lifetime (GD 4 to PND 138) feeding of SPI led to reduced frequency of ACF with 4 or more crypts in the distal colon. Progeny of dams fed SPI only during pregnancy and lactation or progeny fed SPI only after weaning exhibited similarly reduced frequency of large ACF in distal colon. Number of epithelial cells, in the distal colon, undergoing apoptosis was unaffected by diet. SPI reduced weight gain and adiposity, but these were not correlated with fewer numbers of large ACF. Lifetime SPI exposure similarly inhibited development of large ACF in Sprague Dawley rats whose dams were exposed to ethanol during pregnancy. In summary, feeding of SPI to rat dams during pregnancy and lactation suppresses numbers of large ACF in their progeny, implying a long-term or permanent change elicited by the maternal diet. Moreover, results support the use of ACF as an intermediate endpoint for elucidating effects of SPI and its biochemical constituents in colon cancer prevention in rats.

Figure 1

ACF occurrence in proximal and distal colon of Sprague Dawley rats (n = 12) lifetime-fed casein. Shown are means ± SEM of ACF (per rat) containing: 1, 2, 3, 4, 5 or greater than 5 crypts (5+) per ACF; crypt multiplicity (number of aberrant crypts/focus); total number of ACF; and total number of aberrant crypts (no. ACF × crypts/focus). P values indicate all statistically significant differences between proximal and distal colon.

Figure 2

Frequency distribution of ACF in Sprague Dawley rats lifetime-fed SPI or switched, at weaning, from CAS to SPI or from SPI to CAS. Analysis of proximal and distal colon halves is shown. Shown are means ± SEM, per rat, of ACF containing: 1, 2, 3, 4, 5 or greater than 5 crypts (5+) per ACF; crypt multiplicity (number of aberrant crypts/focus); total number of ACF; and total number of aberrant crypts. P value indicates the only statistically significant difference between switchover diets and SPI.

Figure 3

Feeding of casein or SPI to pregnant dams and their progeny elicits differential growth rates. Top panel shows body weight (mean ± SEM) gain in relation to postnatal day (PND) and time of administration of azoxymethane (AOM) for progeny of Sprague Dawley dams. Bottom panel shows divergence in body weights during early postnatal development. P values indicating differences between CAS and SPI groups (t-test) are shown in lower panel.

Figure 4

Dietary protein type influences body fat content. DXA was performed on five animals per group (CAS: casein; SPI: soy protein isolate) at 33 days after the second AOM administration. Means (±SEM) are statistically different for the two diets.

Figure 5

Lack of association of final body weight with ACF size.

Figure 6

Experimental design used for evaluation of diet effects on ACF in progeny of dams exposed to ethanol during pregnancy.

Figure 7

Frequency distribution of ACF in rat progeny lifetime fed casein (n = 10) or SPI (n = 14) and whose dams were exposed to ethanol during pregnancy (Fig. 6). Analysis of proximal and distal colon halves is presented. Shown are mean ± SEM, per rat, of ACF containing: 1, 2, 3, 4, 5 or greater than 5 crypts (5+) per ACF; crypt multiplicity (number of aberrant crypts/focus); total number of ACF; and total number of aberrant crypts. P values indicate statistically significant differences between diets.