Adolescent Vitamin A Intake Alters Susceptibility to Mammary Carcinogenesis in the Sprague-Dawley Rat

Abstract

We tested the hypothesis that adolescent dietary vitamin A intake impacts mammary gland development and subsequent sensitivity to carcinogenesis. Sprague-Dawley rats were fed a purified diet that was vitamin A deficient, adequate (2.2 mg retinyl palmitate/kg diet), or supranutritional (16 mg retinyl palmitate/kg diet) from 21 to 63 days of age, the period of adolescent mammary gland development. At 73 days of age, rats were given 1-methyl-1-nitrosourea (25 mg/kg body wt i.p.) and monitored for mammary tumors. Tumors appeared earlier and more frequently in rats fed vitamin A-deficient or -supplemented diets. Vitamin A deficiency during adolescence was associated with alveolar mammary gland development and precocious milk protein expression, while supplementation was associated with ductal gland development and suppression of milk protein expression. Differences in circulating estradiol and mammary gland estrogen receptor-alpha, and estrogen-responsive progesterone receptor mRNA were not observed, suggesting that the effects of vitamin A on mammary gland development and carcinogenesis are estrogen independent. Mammary expression of another hormone receptor that regulates milk protein expression, the glucocorticoid receptor, was also unaffected. These results demonstrate that vitamin A intake during adolescence alters mammary gland differentiation and indicate that a narrow range of vitamin A intake during adolescence protects against carcinogenesis.

Nutritional Modulation of Terminal End Buds: Its Relevance to Breast Cancer Prevention

“…Other dietary compounds, when exposed during lactation that have been reported to reduce susceptibility to malignant transformation in the mammary gland include low fat n-3 polyunsaturated fatty acids (n-3 PUFA) [12], conjugated linoleic acid (CLA) [13], flaxseed [46], and resveratrol [15]. Deficient or excessive amount of Vitamin A [47] or high fat n-3 PUFA [12] in the prepubertal diet increases mammary tumorigenesis, and an exposure to epigallocatechin-3-gallate (EGCG), the major catechin found in green tea does not modify later chemically induced mammary cancer risk [15]. Studies investigating the effects of CLA [13], vitamin A [47], resveratrol and EGCG [15] on mammary tumorigenesis exposed rats to these compounds either from weaning until the carcinogen exposure or from birth throughout the rest of the study.…”

“…Deficient or excessive amount of Vitamin A [47] or high fat n-3 PUFA [12] in the prepubertal diet increases mammary tumorigenesis, and an exposure to epigallocatechin-3-gallate (EGCG), the major catechin found in green tea does not modify later chemically induced mammary cancer risk [15]. Studies investigating the effects of CLA [13], vitamin A [47], resveratrol and EGCG [15] on mammary tumorigenesis exposed rats to these compounds either from weaning until the carcinogen exposure or from birth throughout the rest of the study. In the other studies, dietary exposures took place before weaning between postnatal postnatal weeks 1 and 3.…”

Retinol Enhances Differentiation of the Gastric Parietal Cell Lineage in Developing Rabbits

“…For example, during development excess vitamin A leads to i) inhibition of keratinization and metaplastic transformation of the epidermis into a mucus-secreting epithelium [8], ii) enhancement of duct cell formation and down regulation of milk protein expression in the mammary glands [9], and iii) alteration of gene expression in tracheobronchial epithelium [10]. In the stomach, while it has been reported that vitamin A plays a cytoprotective role against gastric ulcer [11], Chiba and Arima [12] found that incubation of isolated gastric mucosal cells of newborn rats or young humans with vitamin A for 48 h stimulates acid secretion.…”

Nutritional modulation of the cell cycle and breast cancer

“…In rats, vitamin A-deficient and -supplemented rats develop more carcinogen-induced mammary tumors than animals fed vitamin A-adequate diets (Metz et al 2002).…”