Maternal consumption of canola oil suppressed mammary gland tumorigenesis in C3(1) TAg mice offspring

Abstract

Background: Maternal consumption of a diet high in omega 6 polyunsaturated fats (n-6 PUFA) has been shown to increase risk whereas a diet high in omega 3 polyunsaturated fats (n-3 PUFA) from fish oil has been shown to decrease risk for mammary gland cancer in female offspring of rats. The aim of this study was to determine whether increasing n-3 PUFA and reducing n-6 PUFA by using canola oil instead of corn oil in the maternal diet might reduce the risk for breast cancer in female offspring.

Methods: Female SV 129 mice were divided into two groups and placed on diets containing either 10% w/w corn oil (which is 50% n-6 PUFA, control diet) or 10% w/w canola oil (which is 20% n-6 PUFA, 10% n-3 PUFA, test diet). After two weeks on the diets the females were bred with homozygous C3(1) TAg transgenic mice. Mother mice consumed the assigned diet throughout gestation and nursing of the offspring. After weaning, all female offspring were maintained on the control diet.

Results: Compared to offspring of mothers fed the corn oil diet (CO/CO group), offspring of mothers fed the canola oil diet (CA/CO group) had significantly fewer mammary glands with tumors throughout the experiment. At 130 days of age, the CA/CO group had significantly fewer tumors per mouse (multiplicity); the tumor incidence (fraction of mice with any tumor) and the total tumor weight (per mouse that developed tumor) was less than one half that of the CO/CO group. At 170 days of age, the total tumor weight per mouse was significantly less in the CA/CO group and if a tumor developed the rate of tumor growth rate was half that of CO/CO group. These results indicate that maternal consumption of canola oil was associated with delayed appearance of mammary gland tumors and slowed growth of the tumors that developed.

Conclusions: Substituting canola oil for corn oil is an easy dietary change for people to make; such a change to the maternal diet may decrease risk for breast cancer in the daughter.

Figure 1

Mean body weight gain between 21 and 130 days of age. Body weight gain between 21 and 130 days of age was determined for each mouse. There was no significant difference between the two groups in body weight gain between weaning (21 days) and 130 days of age. CO/CO n = 14; CA/CO n = 17 mice, p = 0.95 by T-test.

Figure 2

Tumor incidence and multiplicity at 130 days of age. A. Tumor incidence (fraction of mice with any tumor) at 130 days of age was not quite significantly different due to the diet of the mother. CO/CO -- 7 of 14 mice had tumors, CA/CO -- 4 of 17 mice had tumors. Fisher's exact test, p = 0.1. B. Tumor multiplicity, the mean number of tumors per mouse at 130 days of age. There were significantly fewer tumors per mouse by Mann-Whitney, p < 0.001. CO/CO n = 14 mice; CA/CO n = 17 mice. C. The total tumor weight per mouse was not quite significantly less in the CA/CO group than in the CO/CO group, p = 0.15 by Mann-Whitney test. CO/CO n = 14 mice; CA/CO n = 17 mice.

Figure 3

Tumor multiplicity at 170 days and growth rate. A. The mean number of tumors per mouse at 170 days was less, but not significantly different, in the CA/CO group (n = 11) than in the CO/CO group (n = 9). B. The tumor weight per mouse at 170 days was significantly less in the CA/CO group (n = 11) than in the CO/CO group (n = 9), p < 0.02 by Mann-Whitney. C. The mean tumor growth rate in the CA/CO group from detection until 170 days of age was 1/2 the growth rate of the CO/CO group.

Figure 4

Glands with tumor per mouse with time. Two way analyses of variance showed that the number of glands with tumor per mouse with time was significantly different due to treatment (p = 0.02) and to time (p = 0.0001). Consumption of the canola oil containing diet by the mothers of these mice significantly decreased the number of glands with tumor. As expected, with time the number of glands with tumor increased in both groups. Number of mice per group at 110, 130, 150 and 170 days of age are: CO/CO - 14, 14, 5, 9, and CA/CO -- 6, 17, 7, 11 respectively.

Figure 5

Results of protein analyses for fatty acid synthase (Fas) and CCAAT/enhancer binding protein (C/EBP), beta at 130 days of age. Western blot for fatty acid synthase showed that Fas protein was significantly less (p = 0.02 by T-test, n = 3/group) and that C/EBP, β was not quite significantly higher (p = 0.06 by T-Test, n = 3/group) in mammary glands of CA/CO mice than in CO/CO mice at 130 days. Values shown are relative density and have been corrected for protein loading (GAPDH) and for cytokeratin (to correct for the epithelial compartment of the assayed sample).