Vitamin D3, Lactose, and Xylitol Stimulate Chromaffin Cell Proliferation in the Rat Adrenal Medulla

Chronic consumption by rats of diets rich in sugars or sugar alcohols leads to an increased incidence of pheochromocytomas. This relationship is hypothesized to be based on altered Ca2+homeostasis due to increased intestinal Ca2+absorption. Other agents associated with pheochromocytomas in rats in l...

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Bibliographic Details
Published in:Toxicology and applied pharmacology 1996-09, Vol.140 (1), p.115-123
Main Authors: Tischler, Arthur S., Powers, James F., Downing, John C., Riseberg, Jocelyn C., Shahsavari, Mehzad, Ziar, Jeffrey, McClain, R.Michael
Format: Article
Language:English
Subjects:
ADRENAL GLANDS
Adrenal Medulla - drug effects
Adrenal Medulla - ultrastructure
Animal tumors. Experimental tumors
Animals
Biological and medical sciences
BLOOD CHEMISTRY
BLOOD COMPOSITION
Body Weight - drug effects
CALCIO
CALCITRIOL
CALCIUM
Calcium - blood
CATION
CATIONES
CATIONS
CELL DIVISION
Cell Division - drug effects
CHOLECALCIFEROL
Cholecalciferol - administration & dosage
Cholecalciferol - pharmacology
Chromaffin Cells - cytology
Chromaffin Cells - drug effects
COMPOSICION DE LA SANGRE
COMPOSITION DU SANG
DIET
DIETA
DIETARY INTAKE
DIVISION CELLULAIRE
DIVISION CELULAR
ESTEROLES
Experimental renal and urinary tract tumors
GLANDULAS SUPRARRENALES
HISTOPATHOLOGIE
HISTOPATHOLOGY
HISTOPATOLOGIA
INTAKE
Kidney - drug effects
Kidney - pathology
KIDNEYS
LACTOSA
LACTOSE
Lactose - administration & dosage
Lactose - pharmacology
Male
Medical sciences
NEOPLASMAS
NEOPLASME
NEOPLASMS
Organ Size - drug effects
PHEOCHROMOCYTOMA
RAT
RATA
RATS
REGIME ALIMENTAIRE
REIN
RINONES
STEROL
STEROLS
SURRENALE
Tumors
VITAMIN D
VITAMINA D
VITAMINE D
XILITOL
XYLITOL
Xylitol - administration & dosage
Xylitol - pharmacology
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Summary:Chronic consumption by rats of diets rich in sugars or sugar alcohols leads to an increased incidence of pheochromocytomas. This relationship is hypothesized to be based on altered Ca2+homeostasis due to increased intestinal Ca2+absorption. Other agents associated with pheochromocytomas in rats in long-term toxicity studies have been shown to increase chromaffin cell proliferation, leading to the suggestion that the tumors occur secondarily to increased chromaffin cell turnover. We have demonstrated marked stimulation of chromaffin cell proliferation by vitamin D3, a potent stimulus to Ca2+absorption not previously associated with adrenal medullary toxicity. This effect is detectable during the first week of dietary supplementation and persists throughout a 4-week time course. Lactose and xylitol, representative of sugars and sugar alcohols associated with pheochromocytomas, are also mitogenic but to a lesser extent, with their effects first detectable during Week 4 of dietary supplementation. Vitamin D3, its active metabolite calcitriol, lactose, and xylitol all fail to stimulate proliferation of rat chromaffin cellsin vitro.The mitogenic effects of these agents may be mediated presynapticallyin vivo.The data suggest that altered Ca2+homeostasis may increase chromaffin cell proliferation and support the hypothesis that diets containing high concentrations of sugars and sugar alcohols cause pheochromocytomas in rats secondarily by this mechanism.
ISSN:0041-008X
1096-0333
DOI:10.1006/taap.1996.0204