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Effect of dietary zinc intake on N-methyl-N-nitrosourea-induced mammary tumorigenesis and tumor histology in sexually mature female Sprague-Dawley rats Lee, Samantha

Abstract

Breast cancer is influenced by many factors such as reproductive history, hormonal, genetic and dietary factors. Zinc is vital to many physiological processes including DNA synthesis and cell proliferation. Increasing evidence has linked zinc exposure to mammary tumorigenesis. The hypothesis of this project was that dietary zinc levels have an effect on chemical carcinogen-induced mammary tumorigenesis in rats. The overall objective was to determine the effects of dietary zinc intake on the induction of mammary tumorigenesis by N-methyl-N-nitrosourea in sexually mature rats. Twenty one-day old female Sprague- Dawley rats were assigned to one of the following dietary treatment groups: low zinc (3 mg zinc/kg diet), adequate zinc (12 mg zinc/kg diet; ad libitum control) or high zinc (155 mg zinc/kg diet) group. In addition, two pair-fed control groups: pair-fed-to the-adequate-zinc and pair-fed-to-the-high-zinc groups, were also included. The rats were fed assigned diets from 21-days. At 50-days of age, all rats were injected with N-methyl-N-nitrosourea (50 mg/kg body weight). Starting from six weeks post-N-methyl-N-nitrosourea injection, rats were palpated weekly to monitor the development of mammary tumors. The experiment was terminated 14 weeks post-N-methyl-N-nitrosourea injection. Mammary tumorigenesis was assessed by tumor incidence, numbers, size, burden, multiplicity and latency of both palpable and total tumors. Tumor grade was assessed histologically. Incidence and number of both palpable and total tumors, and multiplicity of total tumors were lower in marginally low zinc rats than in the ad libitum and pair-fed control rats. Multiplicity of palpable tumors, latency, size and burden were lower in the marginally low zinc and pair-fed rats than in the ad libitum control rats. High zinc intake had no effect on all parameters used to assess the N-methyl-N nitrosourea-induced rat mammary tumorigenesis. Dietary zinc intake had no effect on tumor histological characteristics as only malignant tumors were observed regardless of dietary zinc intake. In summary, marginally low zinc intake reduced N-methyl-N-nitrosourea-induced mammary tumorigenesis in sexually mature female rats. Some of the inhibitory effects of marginally low zinc intake on N-methyl-N-nitrosourea-induced rat mammary tumorigenesis were due to reduced feed intake associated with low zinc intake, rather than low zinc intake per se. Zinc supplementation, however, had no effect on N-methyl-N-nitrosourea-induced rat mammary tumorigenesis.

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