Effects of 3-Methylcholanthrene and Phenobarbital on the Capacity of Embryos to Bioactivate Teratogens During Organogenesis

Details

• Personal Author:
  Fantel AG ; Faustman-Watts EM ; Giachelli CM ; Greenaway JC ; Juchau MR ; Shepard TH
• Description:
  Pregnant Sprague-Dawley rats were divided into four groups and given ip injections of 3-methylcholanthrene (MC) in corn oil, corn oil only, phenobarbital (PB) in Hank's balanced salt solution (HBSS), or HBSS only. Maternal animals were killed on Day 10 of gestation, and embryos from each group were explanted in medium containing cyclophosphamide (CP), 2-acetylaminofluorene (AAF), or dimethylsulfoxide vehicle. After a 24-hr culture period, embryos from dams treated with HBSS, corn oil, or PB/HBSS exhibited no increase in abnormalities (as compared with controls) when either CP or AAF were added to the media. However, embryos transplacentally preexposed to MC and subsequently treated during culturing with AAF (but not CP) exhibited striking increases in malformation incidence. Commonly observed malformations included abnormally open neural tubes, abnormal flexure rotation, and prosencephalic defects. Homogenates of Day 10 embryos transplacentally preexposed to MC exhibited readily measurable oxidative biotransformation of AAF as assessed with HPLC. Biotransformation of AAF by embryos from the other three groups was virtually undetectable. Incorporation of exogenously supplemented bioactivating systems from livers of mature animals indicated that postmitochondrial supernatant fractions (S-9) from male, MC-pretreated rats effectively catalyzed the conversion of AAF (but not CP) to embryotoxic metabolites. Conversely, hepatic S-9 from adult, male, PB-pretreated rats was highly effective in converting CP (but not AAF) to embryotoxic metabolites. The results indicated the inducerspecific occurrence of embryonic bioconversion of AAF to embryotoxic metabolites via MC-inducible, P-450-dependent, embryonic enzyme systems. [Description provided by NIOSH]
• Subjects:
  Animals Energy Metabolism Occupational Health Safety Teratogenesis Toxicology
• Keywords:
  Animal Studies Bioactivation Embryopathology Embryotoxicity Enzymatic Effects In Utero Exposure In Vitro Study Metabolic Effects Pharmacology Teratogens
• ISSN:
  0041-008X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  OSHA Region 10 ; Washington
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  137-146
• Volume:
  80
• Issue:
  1
• NIOSHTIC Number:
  nn:20060474
• Citation:
  Toxicol Appl Pharmacol 1985 Aug; 80(1):137-146
• Contact Point Address:
  Mont R. Juchau, Department of Pharmacology, School of Medicine (SJ-30), University of Washington, Seattle, Wash. 98195
• CAS Registry Number:
  3-Methylcholanthrene (CAS RN 56-49-5)
• Federal Fiscal Year:
  1985
• Peer Reviewed:
  True
• Source Full Name:
  Toxicology and Applied Pharmacology
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:af5f34a5b81948b0d0899117c0f65576561a3fbe10757bf731f3117957059bfa6265ae05143edcd70dc4d9e15d9acf9f022a00a450be5332c18d2ae324f0211b
• Download URL:
  https://stacks.cdc.gov/view/cdc/224351/cdc_224351_DS1.pdf
• File Type:
  [PDF - 592.17 KB ]