HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Nitrofen-induced congenital diaphragmatic defects in CD1 mice.

Abstract
In previous clinical reports, we have documented the association of several morphologic changes with congenital diaphragmatic hernia or, perhaps more appropriately termed, congenital diaphragmatic defect (CDD). These anomalies include decreased cardiac mass with left ventricular hypoplasia in infants with left-sided CDDs (Siebert et al., '84), enlarged, asymmetric chests (Siebert and Benjamin, '87), and extrathoracic anomalies (Benjamin et al., '88), including urinary tract anomalies and elevated kidney weights in otherwise normal kidneys (Glick et al., '90; Siebert et al., '90). Hypoplastic lungs and hearts and enlarged chests are thought to result from the herniation of abdominal viscera into the thoracic cavity, but for the renal abnormalities, pathogenesis is unclear. The findings are intriguing, for they could mirror unrecognized developmental relationships between the diaphragm, lung, heart, and kidney. In order to further examine these issues and to test the applicability of experimentally produced CDDs to human disease, we administered nitrofen (2,4-dichlorophenyl-p-nitrophenyl ether), an herbicide known to produce diaphragmatic defects in rodents, to time-mated CD1 mice by gavage feeding on gestational days 8 and 9. Dosages were 200 (low dose) or 500 (high dose) mg/kg body weight, and fetuses were studied on gestational day 18. Diaphragmatic defects occurred in a dose-response fashion: 0% (0/48) control or sham-fed, 5% (5/104) in the low-dose group, and 25% (19/75) in the high-dose group. Several fetuses with cleft palate, renal agenesis, exencephaly/encephalocele, and/or Di-George sequence were noted at the high dose, the latter a previously undescribed finding. Diaphragmatic defects were primarily right sided and only associated with herniation of abdominal viscera in animals exposed to 500 mg/kg.(ABSTRACT TRUNCATED AT 250 WORDS)
AuthorsD S Wickman, J R Siebert, D R Benjamin
JournalTeratology (Teratology) Vol. 47 Issue 2 Pg. 119-25 (Feb 1993) ISSN: 0040-3709 [Print] United States
PMID8446925 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Herbicides
  • Phenyl Ethers
  • nitrofen
Topics
  • Abnormalities, Drug-Induced (pathology)
  • Animals
  • Body Weight (drug effects)
  • Diaphragm (abnormalities)
  • Dose-Response Relationship, Drug
  • Female
  • Herbicides (toxicity)
  • Maternal-Fetal Exchange
  • Mice
  • Organ Size (drug effects)
  • Phenyl Ethers (administration & dosage, toxicity)
  • Pregnancy

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: