The responses of neurons and glial cells to diphenylhydantoin (DPH), 5-(p- hydroxyphenyl)-5-phenylhydantoin (HPPH) and phenobarbital were studied in cell cultures of dissociated chick embryo brain. Drugs were added to cultures daily for 3 days in concentrations ranging from 1 x 10–4 to 1 x 10–3M. Histological evaluations revealed that cultures treated with DPH exhibited fewer cell aggregates, fewer neurons and less prominent neuronal processes. Preliminary studies suggested that the degree of neurotoxicity might vary in different brain regions and at different stages of neural development. Cultures treated with HPPH exhibited toxicity similar to those treated with DPH but phenobarbital-treated cultures were not significantly different than control cultures. Incorporation of [14C]-leucine into protein was also decreased in cultures treated with DPH but not in those treated with phenobarbital.

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