Epididymal GSH in Chemical-Induced Germ Cell Mutations

Details

• Personal Author:
  Gandy J
• Description:
  The effect of changing concentrations of glutathione (GSH) in the male reproductive tract was investigated using sexually mature male Sprague-Dawley-rats sacrificed at 1, 2, 4, 8, or 16 hours following administration of various test compounds selected for their ability to perturb GSH levels. GSH content was determined in the liver, testes, and epididymides. GSH levels in all tested organs were significantly reduced following administration of isophorone (78591) (500mg/kg), phorone (504201) (250mg/kg), and diethylmaleate (500mg/kg). Isophorone treatment resulted in a significantly enhanced binding of tritium labeled ethyl-methanesulfonate (3H-EMS) to sperm heads. Hepatic and epididymal GSH was reduced following trimethyl-phosphate (512561) (600mg/kg), naphthalene (91203) (500mg/kg), and methyl-iodide (74884) (100mg/kg) administration, but no change was noted in testicular levels. Hepatic GSH was reduced following pentachlorophenol (87865) (25mg/kg) and acetaminophen (103902) (1500mg/kg) exposures, but no changes were apparent in reproductive tract GSH. In an additional study, rats exposed to phorone (250mg/kg) plus EMS showed a significant increase in the mortality of fetal implants during the third week, suggesting that depletion of GSH pools prior to EMS administration potentiated EMS induced dominant lethal clastogenesis. The authors suggest that chemically induced lowering of GSH in the male reproductive tract may be a mechanism for potentiation of chemically induced germ cell mutations. Subsequent tests indicated that treatment with acivicin plus N-acetyl-cysteine served to enhance the levels of GSH in reproductive tissue in-vivo. Studies are being conducted to determine whether this increase will offer protection against the mutagenic effects of ethyl-methanesulfonate. [Description provided by NIOSH]
• Subjects:
  Digestive System Digestive System Diseases Laboratories Liver Mutagens Occupational Health Safety Urogenital Diseases
• Keywords:
  Hepatotoxicity Laboratory-animals Liver-damage NIOSH-Grant Reproductive-system-disorders Spermatozoa
• Series:
  Grant Final Reports
• Publisher:
  National Institute for Occupational Safety and Health
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Final Grant Report
• Place as Subject:
  Arkansas ; OSHA Region 6
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Division:
  OEP - Office of Extramural Programs
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  1-30
• NIOSHTIC Number:
  nn:00184440
• NTIS Accession Number:
  PB89-152607
• Citation:
  Atlanta, GA: U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control, National Institute for Occupational Safety and Health, R03-OH-02258, 1988 Jul; :1-30
• Contact Point Address:
  Pharmacology University of Arkansas 4301 W Markham Little Rock, Ark 72205
• CAS Registry Number:
  Acetaminophen (CAS RN 103-90-2) ; Isophorone (CAS RN 78-59-1) ; Methyl iodide (CAS RN 74-88-4) ; Naphthalene (CAS RN 91-20-3) ; Pentachlorophenol (CAS RN 87-86-5) ; Phorone (CAS RN 504-20-1) ; Trimethyl phosphate (CAS RN 512-56-1)
• Federal Fiscal Year:
  1988
• NORA Priority Area:
  Reproductive System Disorders
• Performing Organization:
  University of Arkansas Med Scis Ltl Rock, Little Rock, Arkansas
• Peer Reviewed:
  False
• Start Date:
  19860501
• Source Full Name:
  National Institute for Occupational Safety and Health
• End Date:
  19880430
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:0f94d8fc8dc3fada2c5862d1e2c1eca977e9ec5279cc13e75705054ac90f7ed124dca4d24248a58e9792171aa99ae154e19d2184ba8eb796e84aee9354cce010
• Download URL:
  https://stacks.cdc.gov/view/cdc/217754/cdc_217754_DS1.pdf
• File Type:
  [PDF - 1.08 MB ]