Early biochemical detection of adverse effects of a neurobehavioral teratogen: influence of prenatal methylmercury exposure on ornithine decarboxylase in brain and other tissues of fetal and neonatal rat.

Ornithine decarboxylase (ODC), an enzymatic regulator of macromolecule synthesis, has proven useful as a biochemical marker for teratologic events. Daily administration of methylmercury (0.5 or 1 mg/kg s.c.) to pregnant rats during the second and third trimesters had a profound effect on ODC in whole fetus that was detectable as early as 13 days of gestation. Levels of enzyme activity in fetal brain also showed a marked increase centered about gestational day 17 as well as a significant elevation during early postnatal life; in the latter case, the cerebellum appeared to be a major target for methylmercury-induced aberrations. These effects were accompanied by little or no alteration in general growth rate, brain weights, or weights of other tissues (liver, heart, lung). Furthermore, no other tissue displayed such dramatic effects on ODC activity. Lowering the dose of methylmercury by an order of magnitude (0.05 to 0.1 mg/kg), levels which are associated with almost purely neurobehavioral effects of the teratogen, still resulted in clear-cut elevations of both whole fetus ODC and fetal and neonatal brain ODC. These results indicate that a sensitive biochemical detection procedure used in the fetus/neonate can successfully predict the subsequent tissue-specific damage to neurotransmitter systems and behavior resulting from methylmercury.

Duke Scholars

Author Theodore Alan Slotkin Pharmacology & Cancer Biology