Journal of Toxicologic Pathology
Online ISSN : 1881-915X
Print ISSN : 0914-9198
ISSN-L : 0914-9198
Short Communications
Stimulation of Adrenal Chromaffin Cell Proliferation by Hypercalcemia Induced by Intravenous Infusion of Calcium Gluconate in Rats
Kaori Isobe, Tsuneo Ito, Shun-ichiro Komatsu, Kentaro Asanuma, Etsuko Fujii, Chie Kato, Kenji Adachi, Atsuhiko Kato, Tetsuro Sugimoto, Masami Suzuki
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Keywords: cell proliferation activity, adrenal glands, chromaffin cell, hypercalcemia, rat, bromodeoxyuridine
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2012 Volume 25 Issue 4 Pages 281-285

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Abstract

Increased incidence of adrenal pheochromocytoma is frequently encountered in rat carcinogenicity studies. In some of the studies, the finding is judged to be due to a rat-specific mechanism of carcinogenesis caused by a disturbance of calcium homeostasis. However, direct evidence that the proliferation of chromaffin cells in the adrenal medulla is induced solely by hypercalcemia is not available. In this study, calcium gluconate was intravenously infused for 7 days to rat chromaffin cells by a tail cuff method, and cumulative labeling with bromodeoxyuridine (BrdU) was carried out to evaluate the proliferative activity. The serum calcium concentration was dose-dependently increased, and a high calcium concentration was stably sustained from day 2 to 7. In the adrenal medulla, BrdU-positive chromaffin cells increased in the calcium gluconate-treated animals, and the BrdU-labeling index increased in a dose-dependent manner. In addition, an increased BrdU-labeling index of chromaffin cells was shown to correlate with the serum calcium concentration. Our results demonstrate that hypercalcemia directly enhances the proliferative activity of chromaffin cells and that the proliferative activity is correlated with the serum calcium concentration.

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© 2012 The Japanese Society of Toxicologic Pathology
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