title: Whole-food sources of vitamin A more effectively inhibit female rat sexual maturation, mammary gland development, and mammary carcinogenesis than retinyl palmitate.
abstract: Previous work using an adolescent rat model for breast cancer showed increased tumor occurrence in rats fed a chemopreventive dose of vitamin A. Preclinical models for nutrient-cancer interactions utilizing defined diets do not replicate the complexity of the human diet and may be inadequate to investigate food patterns associated with reduced cancer risk in humans. To evaluate this concept, the effects of vitamin A on sexual maturation, mammary gland development, and sensitivity to carcinogenesis were determined in the context of a human food-based diet (whole food diet). At 20 d of age (p20), female rats received either a whole-food diet with adequate levels of vitamin A, a diet with a 5.5-fold increase in vitamin A from fruits and vegetables (S diet), or a diet with a 6.2-fold increase in vitamin A provided as retinyl palmitate (RP diet). To determine the effect of dietary intervention on pubertal mammary gland development, the dietary intervention period was restricted to postnatal d 21-63. Rats were injected with 50 mg 1-methyl-1-nitrosourea/kg body weight at d 66. Compared with adolescent rats that consumed the Ad diet, consumption of S and RP diets reduced mammary cancer multiplicity (relative risk approximately 0.7, P < or = 0.002), which was associated with a reduction in alveolar gland development. The S diet suppressed the onset of sexual maturation (P < 0.001) and inhibited markers of mammary alveologenesis more than the RP diet. These data demonstrate that the amount and source of vitamin A consumed by adolescent female rats can influence the onset of puberty, mammary gland alveolar development, and breast cancer risk and highlight the relevance of utilizing whole-food diets to evaluate the role of dietary factors in cancer prevention.
authors.affiliation: Department of Medicine, Division of Medical Oncology and Colorado Cancer Center, University of Colorado Health Science Center, Aurora, CO 80010, USA.
authors.forename: Shauntae M
authors.initials: SM
authors.lastname: McDaniel
authors.forename: Caitlin
authors.initials: C
authors.lastname: O'Neill
authors.forename: Richard P
authors.initials: RP
authors.lastname: Metz
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Tarbutton
authors.forename: Maria
authors.initials: M
authors.lastname: Stacewicz-Sapuntzakis
authors.forename: Jerianne
authors.initials: J
authors.lastname: Heimendinger
authors.forename: Pamela
authors.initials: P
authors.lastname: Wolfe
authors.forename: Henry
authors.initials: H
authors.lastname: Thompson
authors.forename: Pepper
authors.initials: P
authors.lastname: Schedin
mesh_terms: D000818:Animals; D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D004032:Diet; D004224:Diterpenes; D004305:Dose-Response Relationship, Drug; D005260:Female; D008321:Mammary Glands, Animal / Q000254:growth & development*; D015674:Mammary Neoplasms, Animal / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000084562:Retinyl Esters; D046468:Sexual Development / Q000187:drug effects*; D014801:Vitamin A / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology*
chemical_list: D016588:Anticarcinogenic Agents; D004224:Diterpenes; D000084562:Retinyl Esters; D014801:Vitamin A; C014794:retinol palmitate