Citation

Doerge DR, Takazawa RS. Chem. Res. Toxicol. 1990; 3(2): 98-101.

Copyright

(Copyright © 1990, American Chemical Society)

DOI

10.1021/tx00014a003

PMID

2130946

Abstract

Ethylenethiourea (ETU) is a thyroid carcinogen present in foods formed by degradation and metabolism of ethylenebis[dithiocarbamate] fungicides. ETU inhibits thyroid peroxidase (TPX), the enzyme that catalyzes synthesis of thyroid hormones. Inhibition of TPX-catalyzed reactions by ETU occurs only in the presence of iodide ion with concomitant oxidative metabolism to imidazoline and bisulfite ion. Inhibition ceases upon consumption of ETU with no loss of enzymatic activity and negligible covalent binding of ETU to TPX. TPX inhibition by ETU is unlike that for derivatives of imidazoline-2-thione, which cause suicide inactivation via covalent binding to the prosthetic heme group. These results demonstrate a metabolic route for detoxication of ETU in the thyroid and suggest that low-level or intermittent exposure to ETU would have minimal effects on thyroid hormone production.

Language: en

Keywords

Carbon Radioisotopes; Chromatography, High Pressure Liquid; Ethylenethiourea; Hydrogen Peroxide; Iodide Peroxidase; Iodine; Oxidation-Reduction