Epididymal GSH in chemical-induced germ cell mutations.
Department of Pharmacology and Interdisciplinary Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 1988 Jul; :1-30
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.
NIOSH-Grant; Reproductive-system-disorders; Laboratory-animals; Spermatozoa; Liver-damage; Hepatotoxicity; Mutagens;
Pharmacology University of Arkansas 4301 W Markham Little Rock, Ark 72205
78-59-1; 504-20-1; 512-56-1; 91-20-3; 74-88-4; 87-86-5; 103-90-2
Final Grant Report
NTIS Accession No.
Department of Pharmacology and Interdisciplinary Toxicology, University of Arkansas for Medical Sciences, Little Rock, Arkansas
University of Arkansas Med Scis Ltl Rock, Little Rock, Arkansas