Document Detail

Effect of glutathione modulation on molecular interaction of [14C]-chloroacetonitrile with maternal and fetal DNA in mice.
MedLine Citation:
PMID:  8318758     Owner:  NLM     Status:  MEDLINE    
Binding of haloacetonitriles or their reactive metabolites to macromolecules of fetal tissue may be responsible for reproductive toxicity. To investigate the role of glutathione (GSH) in the metabolism and reproductive toxicity of haloacetonitriles, irreversible interaction of chloroacetonitrile (CAN) with maternal uterine and fetal DNA was assessed in a time course study among normal and among glutathione-depleted mice treated with [2-14C]-CAN. GSH was depleted in maternal and fetal tissues by treating of animals with diethylmaleate (DEM) 1 h before [2-14C]-CAN administration. Maternal urinary excretion of thiocyanate was 5 times higher in glutathione-depleted mice than in controls. At 8 and 24 h following [2-14C]-CAN administration, total radioactivity uptake in maternal uterine tissue, amniotic fluid, and fetal tissue was higher in glutathione-depleted mice than in control. Also the interaction of CAN or its reactive metabolites with maternal uterine DNA was enhanced following glutathione depletion. At 24 h after treatment, the covalent binding to DNA in fetal tissue was significantly increased in glutathione depleted mice (205% of control). The magnitude of interaction of CAN in fetal DNA was about 4 times higher than that in uterine DNA. The time course study in either maternal uterine or fetal DNA revealed elevated and persistent levels of covalent binding of [ C]-CAN to DNA at 72 h after treatment. Enhancement of the molecular interaction of CAN in maternal and fetal DNA following GSH depletion indicates an important role for GSH in CAN metabolism.
A A Abdel-Aziz; S Z Abdel-Rahman; A M Nouraldeen; S A Shouman; J P Loh; A E Ahmed
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Reproductive toxicology (Elmsford, N.Y.)     Volume:  7     ISSN:  0890-6238     ISO Abbreviation:  Reprod. Toxicol.     Publication Date:    1993 May-Jun
Date Detail:
Created Date:  1993-08-05     Completed Date:  1993-08-05     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  8803591     Medline TA:  Reprod Toxicol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  263-72     Citation Subset:  IM    
Department of Biochemistry and Pharmacology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
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MeSH Terms
Acetonitriles / metabolism,  pharmacokinetics,  toxicity*
Carbon Radioisotopes / diagnostic use
DNA / drug effects*,  metabolism,  urine
Fetus / drug effects*,  metabolism*
Glutathione / deficiency,  metabolism*
Maleates / pharmacology
Metabolic Detoxication, Drug
Pregnancy Complications / chemically induced*,  metabolism*,  urine
Grant Support
Reg. No./Substance:
0/Acetonitriles; 0/Carbon Radioisotopes; 0/Maleates; 107-14-2/chloroacetonitrile; 141-05-9/diethyl maleate; 70-18-8/Glutathione; 9007-49-2/DNA

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