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Dietary zinc deficiency and supplementation in early life and mammary tumors development in adulthood female rats

ABSTRACT: Zinc deficiency during pregnancy and postnatal life can adversely affect the health and predispose to an increased risk of developing human diseases at adulthood. The present study was designed to evaluate whether dietary zinc deficiency or supplementation during the pregnancy, lactation and juvenile stages interferes with the development of mammary tumors induced by 7,12-dimethylbenzanthracene (DMBA) in female Sprague-Dawley (SD) rats. Pregnant females SD were allocated into three groups: dams received diets containing adequate (35 mg/Kg chow), deficient (3 mg/Kg chow) or supplemented (180 mg/Kg chow) zinc levels during gestational day 10 (GD 10) until the litters weaning. Female offspring were allocated into three groups and received the same diets as their dams until postnatal day (PND) 51. At PND 51, females SD (n=16 each group) received a single dose of DMBA (50 mg/kg, ig) for initiation of mammary carcinogenesis, adequate zinc diets and were euthanized at PND 180. Tumors samples were collected and processed for histological evaluation and microarray analysis. Dietary zinc deficiency induced a significant reduction in female offspring body weight evolution at parturition, weaning and pubertal phases. At late in life, the early in life dietary zinc deficiency or supplementation did not alter the latency, incidence, multiplicity and volume or histological types of mammary tumors in relation to the adequate zinc group, and changed the expression of a small amount of genes. The present findings indicate that early-in life dietary zinc deficiency or supplementation did not significantly modify the susceptibility to development of mammary tumors induced by DMBA.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE86270 | GEO | 2017/04/08

SECONDARY ACCESSION(S): PRJNA341333

REPOSITORIES: GEO

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Project description:Background: Post-menopausal obesity is an established risk factor for breast cancer. Consumption of diets high in fat is known to be highly correlated with obesity. In this, we sought to evaluate the interaction(s) between high fat diet, weight gain and mammary carcinogenesis using an obese-resistant and obese-prone rat model with direct correlates to human disease. Methods: Female obese-prone (OP) and obese-resistant (OR) weanling rats were placed on either a low fat (10% kcal) or a high fat (39% kcal) n-6 polyunsaturated (PUFA) safflower diet for 30 days. At post natal day (PND) 50, global gene expression profiling was performed on microdissected mammary epithlelium from one cohort of rats and another cohort of rats were given a single oral gavage of either 7,12-dimethylbenz[a]anthracene (DMBA at 14 mg/kg) or vehicle. Rats were then maintained on the diets and body weights, food consumption and development of mammary lesions were monitored weekly. Results: The DMBA-treated OR rats on the 39% safflower diet had significantly greater incidence of ductal carcinoma-in-situ (DCIS) lesions and significantly greater DCIS multiplicity than DMBA-treated OR rats on the 10% safflower diet. These differences were not seen in the OP strain. Gene expression analysis of mammary ductal epithelium from OR rats on the high fat diet showed significant upregulation of proliferation-related genes compared to those consuming the low fat safflower diet. Again, these differences were not seen in the OP strain. Conclusion: Our findings indicate that consumption of high fat safflower diet enhances mammary carcinogenesis in an OR rat strain through increased proliferation of mammary epithelium at the time of exposure, but not in the OP rat strain. Thus, the diet-induced increase in sensitivity was strain-specific and independent of weight gain or obesity level. Female obese-prone (OP) and obese-resistant (OR) weanling rats were placed on either a low fat (10% kcal) or a high fat (39% kcal) n-6 polyunsaturated (PUFA) safflower diet for 30 days. At post natal day (PND) 50, global gene expression profiling was performed on microdissected mammary epithlelium from one cohort of rats and another cohort of rats were given a single oral gavage of either 7,12-dimethylbenz[a]anthracene (DMBA at 14 mg/kg) or vehicle. Rats were then maintained on the diets and body weights, food consumption and development of mammary lesions were monitored weekly.

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Dietary zinc deficiency and supplementation in early life and mammary tumors development in adulthood female rats

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