High-dose dietary zinc promotes prostate intraepithelial neoplasia in a murine tumor induction model

Abstract

To evaluate the role of high-dose dietary zinc in the process of prostate malignancy, 60 Sprague-Dawley rats were randomly divided into four groups: tumor induction with carcinogen and hormone (group 1), oral zinc administration without tumor induction (group 2), oral zinc administration with tumor induction (group 3) and a control without zinc administration or tumor induction (group 4). Zinc was supplied orally in the form of zinc sulfate heptahydrate dissolved in drinking water to groups 2 and 3 for 20 weeks. Although the serum level of zinc measured at 20 weeks was maintained similarly in each group (P = 0.082), intraprostatic zinc concentrations were statistically different. Group 1 prostates contained the least amount of zinc in both the dorsolateral and ventral lobes at levels of 36.3 and 4.8 microg g(-1), respectively. However, in group 3, zinc levels increased in both lobes to 59.3 and 12.1 microg g(-1), respectively, comparable with that of group 4 (54.5 +/- 14.6 and 14.1 +/- 2.4 microg g(-1)). In spite of these increases in zinc concentration, the prevalence of prostate intraepithelial neoplasm was rather increased in group 3 (53.3% and 46.7%) compared with group 1 (33.3% and 33.3%) in both dorsolateral and ventral prostate lobes. Although prostate intraepithelial neoplasm did not develop in any prostate in group 4, zinc administration did induce prostate intraepithelial neoplasm in group 2 (46.7% and 40.0%). Thus, although high dietary zinc increased intraprostatic zinc concentrations, it promoted, instead of preventing, prostate intraepithelial neoplasm in a murine prostate malignancy induction model.

Figure 1

(A): Histological appearance of normal ventral prostate. A single layer of flattened and cuboidal epithelial cells lines the tubules with secretion in the lumen. Epithelial tubules, surrounded by a thin layer of smooth muscle cells, are distributed within the loosely organized stroma. Hematoxylin and eosin (H&E) stained (× 100). Hyperplasia with dysplasia of the dorsolateral prostate (B): columnar cells with increased growth of papillary epithelial cells are shown. Relatively decreased stroma was observed within the papillary projections, compared with normal prostate. H&E stained (× 100). Prostatic intraepithelial neoplasia of ventral prostate (C): prominent papillary projection with an increased complexity of the gland is shown. Nuclei were elongated and demonstrated hyperchromatic change. H&E stained (× 200). Bars = 100 μm.

Figure 2

Zinc concentration in dorsolateral (A) and ventral (B) lobes of the prostate in each treatment group. ^*P < 0.05, comparison between groups 1 and 3; ^#P > 0.05, comparison between groups 3 and 4.