Induction of cellular DNA synthesis in the pancreas and kidneys of rats by peroxisome proliferators, 9-cis retinoic acid, and 3,3',5-triiodo-L-thyronine

We recently suggested that peroxisome proliferators (PPs), 3,3',5-triiodo-L-thyronine (T3), and 9-cis retinoic acid (9-cis RA) induce hepatocyte proliferation in rats through the activation of their nuclear receptors, PP-activated receptors, T3 receptors, and retinoid X receptors. To test wheth...

Full description

Saved in:
Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 1997-03, Vol.57 (5), p.795-798
Main Authors: OHMURA, T, KATYAL, S. L, LOCKER, J, LEDDA-COLUMBANO, G. M, COLUMBANO, A, SHINOZUKA, H
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Bromodeoxyuridine
Cell Division - drug effects
DNA - biosynthesis
Drug toxicity and drugs side effects treatment
Hypolipidemic Agents - pharmacology
Kidney - cytology
Kidney - drug effects
Male
Medical sciences
Microbodies - drug effects
Miscellaneous (drug allergy, mutagens, teratogens...)
Mitogens - pharmacology
Pancreas - cytology
Pancreas - drug effects
Pharmacology. Drug treatments
Pyrimidines - pharmacology
Rats
Rats, Wistar
Signal Transduction
Tretinoin - pharmacology
Triiodothyronine - pharmacology
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:We recently suggested that peroxisome proliferators (PPs), 3,3',5-triiodo-L-thyronine (T3), and 9-cis retinoic acid (9-cis RA) induce hepatocyte proliferation in rats through the activation of their nuclear receptors, PP-activated receptors, T3 receptors, and retinoid X receptors. To test whether nuclear hormone receptor-mediated cell proliferation can be observed in organs other than liver, we examined the effects of these agents on the pancreas and kidneys of male Wistar rats using BrdUrd immunohistochemistry. A single s.c. injection of T3 (2 mg/kg) and single intragastric administration of 9-cis RA (40 mg/kg) or 4-chloro-6-(2, 3-xylidino)-2-pyrimidinylthio-(N-beta-hydroxyethyl) acetamide (200 mg/kg) induced a wave of DNA synthesis in the pancreatic acinar cells and in the proximal tubular epithelial cells of the kidneys, peaking after 24 h. No stimulation of DNA synthesis was observed in ductal or islet cells of the pancreas and in glomeruli of the kidneys. All-trans-retinoic acid, a ligand for retinoic acid receptor, at a dose (200 mg/kg) that induced hepatocyte proliferation, had no effects on cell proliferation of the pancreas and the kidneys. The results suggest that T3, 9-cis RA, and PP activate genes that regulate cell proliferation in target cells through receptor-mediated pathways and initiate cellular DNA synthesis.
ISSN:0008-5472
1538-7445