Methanol-induced neural tube defects in mice: Characterization of lesions, target and teratogen

Thesis/Dissertation · Fri Jan 01 04:00:00 EST 1993

OSTI ID:5544823

Bolon, B N

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.

• Research Organization: Duke Univ., Durham, NC (United States)
• OSTI ID: 5544823
• Country of Publication: United States
• Language: English

Related Subjects

550800 -- Morphology
550900 -- Pathology
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALCOHOL FUELS
ALCOHOLS
ANIMAL CELLS
AUTOMOTIVE FUELS
CARBOXYLIC ACID SALTS
FORMATES
FUELS
HYDROXY COMPOUNDS
METHANOL
METHANOL FUELS
NERVE CELLS
ORGANIC COMPOUNDS
PATHOGENESIS
PATHOLOGICAL CHANGES
SOMATIC CELLS
SYNTHETIC FUELS
TOXICITY