This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Jacob, S. Articles by Ahmed, A. E. Search for Related Content PubMed PubMed Citation Articles by Jacob, S. Articles by Ahmed, A. E. Social Bookmarking                         What's this?

Effect of Glutathione Modulation On the Distribution and Transplacental Uptake of 2-[14C]-Chloroacetonitrile (Can) Quantitative Whole-Body Autoradiographic Study in Pregnant Mice

Department of Pathology University of Texas Medical Branch Galveston, Texas, sjacob.utmb.edu

Abdel-Aziz H. Abdel-Aziz

Department of Pharmacology & Toxicology Faculty of Pharmacy Al-Azhar University Cairo, Egypt

Samia A. Shouman

Department of Cancer Biology National Cancer Institute Cairo University Cairo, Egypt

Ahmed E. Ahmed

Department of Pathology University of Texas Medical Branch Galveston, Texas

Chloroacetonitrile (CAN), a drinking water disinfectant by-product, has mutagenic and carcinogenic properties. CAN is known to deplete glutathione (GSH), and previous studies reported an enhanced molecular interaction of CAN after GSH depletion in the uterine and fetal tissues of mice. The present report may help to understand the potential mechanisms involved in such molecular interactions by examining the disposition, transplacental uptake and covalent interaction of the chemical in normal and GSH depleted pregnant mice (at 13^th day of gestation). Both normal and GSH depleted (by administration of Diethylmaleate (DEM), 0.6 mL/kg, i.p.) pregnant mice were given an equitoxic i.v. dose of 2-[¹⁴C]-CAN (333 µCi/kg equivalent to 77 mg/kg). Animals were processed for whole-body autoradiography (WBA) at 1, 8 and 24 hr after treatment. Tissue distribution of radioactivity in the autoradiographs was quantitated using computer aided image analysis. With few exceptions, a rapid high uptake (at I hr) of radioactivity was observed in all major maternal (liver, lung, urinary bladder, gastrointestinal mucosa, cerebellum, uterine luminal fluid) and fetal (liver, brain) organs of both normal and GSH depleted mice. This pattern of distribution was observed, with lesser intensity, at 8 hr following treatment. At a later time period (24 hr), there was a significant higher retention and covalent interaction of radioactivity in GSH depleted mouse tissues especially in the liver as compared to normal mouse. This study suggests that 2-[¹⁴C]-CAN and/or its metabolites are capable of crossing the placental barrier. The observed higher uptake and retention of the radioactivity in the maternal liver, kidney, cerebellum, nasal turbinates and fetal liver may pose toxicity of the chemical to these organs. The increased covalent interaction of radioactivity in GSH depleted mice liver may indicate the potential utilization of GSH pathway by this organ in the detoxication of CAN derived metabolites and thus exerting hepatotoxicity.

Key Words: chloroacetonitrile • covalent interaction • glutathione depletion • haloacetonitriles • quantitative image analysis • reproductive toxicity • transplacental uptake • water disinfectant by-products • whole-body autoradiography.

Toxicology and Industrial Health, Vol. 14, No. 4, 533-546 (1998)
DOI: 10.1177/074823379801400404


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				A. Ahmed, H. El-Mazar, A. Nagy, and A. Abdel-Naim Chloroacetonitrile induces intrauterine growth restriction and musculoskeletal toxicity in fetal mouse Toxicology and Industrial Health, September 1, 2008; 24(8): 511 - 518. [Abstract] [PDF]