Decreased ornithine decarboxylase in the fetal hydantoin syndrome

The anticonvulsant diphenylhydantion (DPH) causes embryonic folate antagonism in the animal model of the fetal hydantoin syndrome. Thus, comparisons were made between the metabolic effects of the teratogens DPH and 9-methyl pteroylglutamic acid (9-methyl PGA), a folate antagonist. The DPH inhibited ornithine decarboxylase (ODC), the rate-limiting enzyme in putrescine biosynthesis, and caused reduced levels of this precursor diamine as well as the resultant polyamines, spermidine and spermine. In contrast, embryos from rats treated with 9-methyl PGA had ODC activity similar to controls and increased levels of putrescine, spermidine, and spermine. Because ODC is an enzyme of major importance for embryogenesis, any alterations in ODC activity may indicate abnormal development.