Effect of glutathione modulation on molecular interaction of [14C]-chloroacetonitrile with maternal and fetal DNA in mice

Abdel Aziz H. Abdel-Aziz, Sherif Z. Abdel-Rahman, Amr M. Nouraldeen, Samia A. Shouman, Jian P. Loh, Ahmed E. Ahmed

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

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 [214C]-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 [14C]-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.

Original languageEnglish (US)
Pages (from-to)263-272
Number of pages10
JournalReproductive Toxicology
Volume7
Issue number3
DOIs
StatePublished - Jan 1 1993
Externally publishedYes

Keywords

  • DNA
  • chloroacetonitrile
  • fetal tissue
  • glutathione
  • haloacetonitriles
  • pregnancy
  • reproductive toxicity
  • uterine tissue
  • water disinfectant by-products

ASJC Scopus subject areas

  • Toxicology

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