Effect of methyl iodide on deiodinase activity.
Methyl iodide (MeI) has been proposed as an alternative for methyl bromide in pre-plant soil fumigation applications that does not affect stratospheric ozone. Preliminary studies in rabbits noted fetal resorptions if the pregnant does were exposed to MeI during a critical period during gestation. In addition, abnormalities in thyroid hormone parameters were also observed in animals exposed to MeI. Since monodeiodination is the major metabolic pathway of the thyroid hormones, we examined the effect of MeI on deiodinase activity as a possible etiology for the alteration in thyroid hormone parameters and ultimate fetal demise. In vitro studies using tissue microsomes and cell culture showed that MeI has no effect on type I 5'-deiodinase (D1) or type II 5'-deiodinase (D2) at physiologically relevant concentrations. At high concentrations (>10 mM,>10,000 ppm), MeI caused a nonspecific inactivation of D1 and D2. Analysis of D1 and D2 activity in rats exposed by inhalation to increasing concentrations of MeI showed a significant decrease in enzyme activity at 100 ppm, while brain type III 5'-deiodinase (D3) was unaffected by MeI at the exposures studied. While the drop in D1 can be explained by the induction of a hypothyroid state in the exposed rats, there is no clear explanation for the fall in D2 levels. In the rabbit studies, there was a significant decrease in kidney D1 in the adult rabbits exposed to 20 ppm MeI. However, there was no effect on liver D1, brain D2, or placental D3 in the MeI-exposed rabbits. Similarly, there was no effect of MeI on fetal D1 or D2 activity. The lack of a significant direct effect of MeI on deiodinase activity and the absence of a change in placental or fetal deiodinase activity make it unlikely that alterations in deiodinase activity plays a role in the fetal resorptions in the MeI-exposed rabbits.
Farwell
Alan P
AP
Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA. alan.farwell@umassmed.edu
Leonard
Jack L
JL
D000818:Animals; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D005260:Female; D047109:Fetal Development / Q000187:drug effects / Q000502:physiology; D006847:Hydrocarbons, Iodinated / Q000633:toxicity*; D019570:Inhalation Exposure / Q000009:adverse effects; D007453:Iodide Peroxidase / Q000378:metabolism*; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D011247:Pregnancy; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D000097564:Iodothyronine Deiodinase Type II
D006847:Hydrocarbons, Iodinated; D007453:Iodide Peroxidase; D000097564:Iodothyronine Deiodinase Type II; C014055:methyl iodide; C109812:iodothyronine deiodinase type I; C117274:iodothyronine deiodinase type III