Effects of Actinomycin D on the Central Nervous System of Higher Animals

Abstract

When a dose of actinomycin D was intrathecally injected into higher animals (dogs and cats), these animals experienced generalized seizures after a latent period of several days.
The critical seizure producing quantity was 0.025mg on the dog. Actinomycin D combines with DNA in the nervous tissue of the brain, this may be the cause of the seizure effect.
When the same dose (0.025mg) of actinomycinic acid, which has a chemical structure resembling that of actinomycin D, but does not combine with DNA in the tissue, was injected into the cerebro-spinal fluid of the dog, the animals did not show any behavioural change.
Electroencephalographic studies of the actinomycin D seizure were carried out on the cat. Several days after the administration of actinomycin D, the animal showed the typical generalized seizure discharges. A generalized seizure discharge induced by actinomycin D began with the occurrence of frequent spikes in group in all of recording sites, then the repetition of a spike and wave complex or a polyspike and wave complex followed. The intervals of each spike and wave complex gradually grew longer, and the seizure discharge stopped.
After the actinomycin D administration, the electroencephalogram sometimes showed remarkable spike discharges occurring in the hippocampal region. They occurred mostly in hippocampus, but to a lesser degree spike discharges occurred in the other regions.
In the preconvulsive state after the actinomycin D administration, regular waves of 8 cps occasionally appeared simultaneously with the occurrence of myoclonic jerks.
In the case of the injection of actinomycinic acid into the cat, no significant change occurred on the electroencephalogram.
However, the injection of DNA into the cerebrospinal fluid, simultaneously performed, with the injection of actinomycin D, did not stop the seizure effect of the latter.
Methionine sulfoximine, characterized by a seizure effect with a long latent period, was also injected into the cerebro-spinal fluid of the dog. The critical seizure producing quantity was 0.18mg. These two convulsants with long latent period, the actinomycin D and the methionine sulfoximine, did not produce seizure effects when combined in different proportions.
Three butyric acid derivatives (GABA, GABOB and S-GABA) did not arrest the actinomycin D seizure effect.