Comparative Studies of Chromaffin Cell Proliferation in the Adrenal Medulla of Rats and Mice

• Published in: Fundamental and applied toxicology 1997-02, Vol.35 (2), p.216-220
• Main Authors: Tischler, Arthur S., Powers, James F., Shahsavari, Mehzad, Ziar, Jeffrey, Tsokas, Panayiotis, Downing, John, McClain, R.Michael
• Format: Article
• Language: English
• Subjects: Adrenal Gland Neoplasms - pathology; Adrenal Medulla - cytology; Adrenal Medulla - pathology; Adrenal Medulla - physiology; Animals; Antihypertensive Agents - pharmacology; Antimetabolites; Biological and medical sciences; Bromodeoxyuridine; Cell Division - drug effects; Cell Division - physiology; Cells, Cultured; Chromaffin Cells - drug effects; Chromaffin Cells - physiology; Drug toxicity and drugs side effects treatment; Female; Male; Medical sciences; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Miscellaneous (drug allergy, mutagens, teratogens...); Pharmacology. Drug treatments; Pheochromocytoma - pathology; Rats; Rats, Inbred F344; Reserpine - pharmacology
• ISSN: 0272-0590; 1095-6832
• DOI: 10.1006/faat.1996.2277

Spontaneous and drug-induced pheochromocytomas are common in rats and rare in mice. The antihypertensive drug reserpine has been shown to both induce pheochromocytomas and stimulate chromaffin cell proliferation in rats, leading to the hypothesis that reserpine causes pheochromocytomas indirectly by providing a proliferative setting in which DNA damage may occur. The present investigation was undertaken to obtain baseline information on the relationship across species between chromaffin cell proliferation and pheochromocytomas. Basal chromaffin cell proliferation was compared in age-matched young adult mice and rats. In addition, mice were studied for adrenal medullary responses to reserpine, and mouse chromaffin cellsin vitrowere studied for responses to agents that are mitogenic for cultured rat chromaffin cells. Concurrently maintained F-344 rats and several strains of mice showed no significant difference in basal BrdU incorporation over a 1-week period. Mice also showed an adrenal medullary proliferative response to reserpine that was comparable to the response previously reported for rats. However, there was a marked disparity between rat and mouse chromaffin cellsin vitro,and cultured mouse chromaffin cells did not respond to any mitogens. Thein vivodata indicate that interspecies differences in basal- or reserpine-stimulated chromaffin cell proliferation sufficient to account for different frequencies of pheochromocytomas are not detectable at a single time point in young adult animals. However, the possibility that such differences might emerge with aging has not been ruled out. These data further suggest either that stimulation of chromaffin cell proliferation might be necessary but not sufficient for development of pheochromocytomas or that stimulated proliferation in mice might not be sustained. The inability of cultured mouse chromaffin cells to respond to mitogens raises the speculation of whether mechanisms that prevent proliferation of normal chromaffin cellsin vitromight also help to protect mice from developing pheochromocytomas.