Thyroid peroxidase as toxicity target for dithiocarbamates.
In vivo ethylenebisdithiocarbamates and ETU are toxic to the thyroid gland. Since the molecular target of these compounds is thought to be thyroid peroxidase (TPO) which catalyzes the transfer of iodine to thyroglobulin, we examined the effect of these compounds on peroxidative activity in Chinese hamster ovary (CHO) cells transfected with the human TPO gene. The activity was inhibited by 50 microM ETU, 5 microM ziram and 5 microM zineb, the last-mentioned effect being irreversible in the absence of iodide. Thiram had no effect. By contrast, the iodinating activity of TPO was blocked only by 5 microM ETU and 50 microM zineb but not by the other compounds. The effect on TPO-catalysed iodination could explain the differences in thyrotoxicity of these compounds in vivo.
Marinovich
M
M
Laboratory of Toxicology, University of Milan, Italy.
Guizzetti
M
M
Ghilardi
F
F
Viviani
B
B
Corsini
E
E
Galli
C L
CL
D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology; D016466:CHO Cells; D002478:Cells, Cultured; D006224:Cricetinae; D005100:Expectorants / Q000378:metabolism; D006139:Guaiacol / Q000378:metabolism; D006801:Humans; D007453:Iodide Peroxidase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007455:Iodine / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008713:Methimazole / Q000494:pharmacology; D010084:Oxidation-Reduction; D013859:Thiocarbamates / Q000633:toxicity*; D014162:Transfection
D013956:Antithyroid Agents; D005100:Expectorants; D013859:Thiocarbamates; D008713:Methimazole; D006139:Guaiacol; D007455:Iodine; D007770:L-Lactate Dehydrogenase; D007453:Iodide Peroxidase