Effect of glutathione modulation on molecular interaction of [14C]-chloroacetonitrile with maternal and fetal DNA in mice.
作者： Abdel-Aziz H. Abdel-Aziz , Sherif Z. Abdel-Rahman , Amr M. Nouraldeen , Samia A. Shouman , Jian P. Loh
DOI: 10.1016/0890-6238(93)90233-W
关键词: DNA 、 Endocrinology 、 Toxicity 、 Internal medicine 、 Biology 、 Reproductive toxicity 、 Fetus 、 Amniotic fluid 、 Uterus 、 Metabolism 、 Glutathione
摘要: Binding of haloacetonitriles or their reactive metabolites to macromolecules fetal tissue may be responsible for reproductive toxicity. To investigate the role glutathione (GSH) in metabolism and toxicity haloacetonitriles, irreversible interaction chloroacetonitrile (CAN) with maternal uterine DNA was assessed a time course study among normal glutathione-depleted mice treated [2-14C]-CAN. GSH depleted tissues by treating animals diethylmaleate (DEM) 1 h before [2-14C]-CAN administration. Maternal urinary excretion thiocyanate 5 times higher than controls. At 8 24 following administration, total radioactivity uptake tissue, amniotic fluid, control. Also CAN its enhanced depletion. after treatment, covalent binding significantly increased (205% control). The magnitude about 4 that DNA. either revealed elevated persistent levels [ C]-CAN at 72 treatment. Enhancement molecular depletion indicates an important metabolism.
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