||Health Effects Research Lab., Research Triangle Park, NC. Perinatal Toxicology Branch. ;Northrop Services, Inc./Environmental Sciences, Research Triangle Park, NC. ;Duke Univ. Medical Center, Durham, NC. Dept. of Pharmacology.
DFMO (alpha-difluoromethylornithine) is a specific irreversible inhibitor of ornithine decarboxylase (ODC), a key enzyme in the biosynthesis of polyamines, which in turn control macromolecule synthesis during cell proliferation. The current study was designed to investigate the effects of inhibition of ODC during discrete prenatal periods on renal growth and function. Five doses of 500 mg/kg DFMO or saline s.c. were administered to timed pregnant Sprague-Dawley rats at 12 hr intervals beginning on gestation days (GD) 11, 14, or 17. Half the dams were killed on GD 20 for fetal morphological analyses and half were allowed to go to term. Renal function was assessed on postnatal days (PD) 3, 6, 10, and 14 by tests of basal renal clearance and urinary concentrating ability, and on PD 42-44 serum chemistries were measured. All three gestational treatment regiments resulted in postnatal deficits in general growth. These data indicate that general tissue growth is not always a predictor of physiological development and support the necessity of multifaceted approaches to the understanding of adverse developmental effects. (Copyright (c) 1989 Alan R. Liss, Inc.)