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Title Methanol-induced neural tube defects in mice: Characterization of lesions, target and teratogen
Creator/Author Bolon, B.N.
Publication Date1993 Jan 01
OSTI IdentifierOSTI ID: 5544823
Resource TypeMiscellaneous
Resource RelationThesis (Ph.D.)
Research OrgDuke Univ., Durham, NC (United States)
Subject560300 -- Chemicals Metabolism & Toxicology ;550800 -- Morphology ;550900 -- Pathology; METHANOL-- TOXICITY;NERVE CELLS-- PATHOLOGICAL CHANGES; AUTOMOTIVE FUELS;FORMATES;METHANOL FUELS;PATHOGENESIS
Related SubjectALCOHOL FUELS;ALCOHOLS;ANIMAL CELLS;CARBOXYLIC ACID SALTS;FUELS;HYDROXY COMPOUNDS;ORGANIC COMPOUNDS;SOMATIC CELLS;SYNTHETIC FUELS
Description/Abstract The present studies investigated the hypothesis that methanol induces neural tube defects (e.g., exenephaly) through the cytotoxic action of its metabolite, formate, upon embryonic neuroepithelium during neurulation.^Methanol was tested because of concerns raised by the proposed heavier use of this alcohol in automobile fuels, which could result in increased exposure of the general public.^Neurulation (gestational days [GD] 7-9 in mice) was shown to be the period of greatest vulnerability.^Pregnant mice inhaled methanol (5,000 to 15,000 ppm) for 6 hr/day either during GD 7-9 or during a encephaly was observed only if exposure to [>=] 10,000 ppm encompassed GD 7 and/or GD 8. Aberrant neural tube closure was confirmed as the pathogensis by demonstrating persistent patency of the anterior neuropore in embryos.^Peak concentrations of 431 mmol methanol/kg and 14 mmol formate/kg were measured in embryos following maternal methanol inhalation at a teratogenic level (15,000 ppm for 6 hr on GD 8).^Autoradiography of pregnant mice after intravenous injection with 0.06 or 6 mmol [sup 14]C-formate/kg on GD 8 revealed selective localization of radioactivity to the neuroepithelium within 10 minutes after administration, with at least a two fold greater level in each tissue of formate-exposed embryos.^Exposure in vitro to either 187 mM methanol or [>=]12 mM formate for 12 hr delayed closure of the anterior neuropore in neurulating mouse embryos.^In addition, in vitro exposure to formate resulted in lower reduction of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bormide (MTT) and decreased levels of ATP in cephalic tissues of embryos.^Formate also reduced MTT staining in neuroepithelium and mesoderm, suggesting these embryonic tissues as potential targets.
PublisherDurham, NC (United States) ;Duke Univ.
Country of PublicationUnited States
LanguageEnglish
FormatPages: (236 p)
AvailabilityUniversity Microfilms, P.O. Box 1764, Ann Arbor, MI 48106 (United States). Order No. 93-32,208
System Entry Date2001 May 13

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