Effects of eflornithine hydrochloride (DFMO) on fetal development in rats and rabbits

Teratology
B A O'TooleJ P Gibson

Abstract

Eflornithine hydrochloride (DFMO) is a highly selective, enzyme-activated, irreversible inhibitor of the enzyme L-ornithine decarboxylase (ODC). Because of its role in the biosynthetic pathway of polyamines, ODC is essential for the growth and development of newly implanted embryonic tissue. In order to assess its effect on embryonic growth and fetal development, at various stages of gestation, DFMO was administered in the drinking water to pregnant rats and rabbits at several concentrations (from 0.03% to 3.0%) and times (from days 7, 10, or 11 through days 18 or 19). Rats were killed on day 21 and rabbits on day 29 of pregnancy (day 1 = day of insemination), and the implantations and fetuses were examined. At a concentration of 1.0% (approximately 1,270 mg/kg/day) in rats and 3.0% (approximately 915 mg/kg/day) in rabbits, maternal food and water consumption and body weight gain were significantly reduced during the treatment period, and all implantations were aborted or resorbed. At lower doses (approximately 200-600 mg/kg/day) fetuses survived to term, though in reduced numbers, and a marked reduction in average fetal weight was seen. At levels of 60 mg/kg/day or lower, there were no deleterious effects to the dams or their ...Continue Reading

References

Dec 1, 1973·Teratology·C A Kimmel, J G Wilson
Aug 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·G D LukS B Baylin
Dec 1, 1983·Experimental and Molecular Pathology·J T YarringtonJ P Gibson
Nov 1, 1982·The American Journal of Physiology·A E Pegg, P P McCann
Jan 1, 1983·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·T A SlotkinF J Seidler
Jan 1, 1983·International Journal of Developmental Neuroscience : the Official Journal of the International Society for Developmental Neuroscience·T A SlotkinJ Bartolome

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Citations

Jan 27, 2009·Birth Defects Research. Part B, Developmental and Reproductive Toxicology·Gladys Chirino-GalindoMartín Palomar-Morales
Dec 31, 1997·The Journal of Veterinary Medical Science·M BonkobaraK Ono
Jul 28, 2011·Endocrine Reviews·Pavine L C LefèvreBruce D Murphy

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