Critical periods for the role of ornithine decarboxylase and the polyamines in growth and development of the rat: Effects of exposure to α‐difluoromethylornithine during discrete prenatal or postnatal intervals
- 1 January 1983
- journal article
- Published by Wiley in International Journal of Developmental Neuroscience
- Vol. 1 (2), 113-127
- https://doi.org/10.1016/0736-5748(83)90038-2
Abstract
The roles of ornithine decarboxylase (ODC) and the polyamines in fetal and neonatal development were examined through the use of α-difluoromethylornithine (DFMO), a specific irreversible inhibitor of ODC. Administration to pregnant rats of 500 mg/kg of DFMO every 12 h for a 4-day period (8 DFMO injections) resulted in fetal and neonatal death; DFMO early in gestation produced fetal resorption whereas late gestational exposure did not compromise fetal viability but instead resulted in a delayed toxic effect, with high mortality in the first postnatal week. Generalized toxicity of DFMO was not apparent in later developmental periods, as 4 days of DFMO treatment begun postnatally did not produce any neonatal death. Shortening the course of gestational DFMO treatment to 2.5 days (5 DFMO injections) also did not adversely affect fetal or neonatal viability and thus permitted identification of critical periods in which various tissues are sensitive to DFMO. Examination of growth patterns of brain, heart and kidney and of neurochemical development of central and peripheral catecholaminergic neurons indicated that different critical periods exist for effects of DFMO on each tissue or even on the various cell types within a tissue. The separable sensitivities were apparent even though the effects of DFMO on ODC and the polyamines for any given treatment period were fairly uniform in all tissues studied. These results indicate that the ODC/polyamine system plays multiple roles in fetal survival and in tissue growth during discrete periods of development; because the time course of cellular maturation differs for each tissue or cell population, DFMO administered during any one brief period can produce organ-specific developmental deficits.Keywords
This publication has 23 references indexed in Scilit:
- Organ specificity of neonatal methyl mercury hydroxide poisoning in the rat: Effects on ornithine decarboxylase activity in developing tissuesToxicology Letters, 1982
- Role of polyamines in isoproterenol-induced cardiac hypertrophy: Effects of α-difluoromethylornithine, an irreversible inhibitor of ornithine decarboxylaseJournal of Molecular and Cellular Cardiology, 1982
- Maturation of growth hormone stimulation of kidney ornithine decarboxylase in the ratLife Sciences, 1982
- Role of Ornithine Decarboxylase in Cardiac Growth and HypertrophyScience, 1980
- L-Ornithine Decarboxylase: an Essential Role in Early Mammalian EmbryogenesisScience, 1980
- Ornithine decarboxylase as a tool in developmental neurobiologyLife Sciences, 1979
- Perinatal methadone addiction affects brain synaptic development of biogenic amine systems in the ratLife Sciences, 1979
- DETERMINATION OF CATECHOLAMINES IN RAT BRAIN PARTS BY REVERSE‐PHASE ION‐PAIR LIQUID CHROMATOGRAPHYJournal of Neurochemistry, 1978
- Regulation of Autonomic DevelopmentAnnual Review of Neuroscience, 1978
- Developmental changes in rat adrenal tyrosine hydroxylase, dopamine-β-hydroxylase and catecholamine levels: Effect of denervationDevelopmental Biology, 1972