Chromosome Studies on the Effect of Primidon (MylepsinumR) and Its Metabolites, Phenobarbital and Phenylethylmalondiamide, in Vitro

Abstract

SummaryPrimidone and its metabolites Phenobarbital and Phenylethylmalondiamide were tested in cultures of human lymphocytes on possible effects of inducing chromosome aberrations. The substances examined ranged from concentrations lower than the therapeutic serum level to 10-75 times this value, which differed with the various substances. Phenylethylmalondiamide shows, besides an increase of spiralization defects at higher concentrations, which was typical for all three substances, no reaction on the chromosome structure.By using the Friedman-test a statistically significant difference (P < 5%) could be found between the average aberration rates of the controls and the cultures which had been treated with Primidone and Phenobarbital. The test according to Wilcoxon and Wilcox shows that there is a statistically significant (P < 5%) difference between the aberration rates of controls and the respectively treated cultures. The higher values for percentage of aberrant mitoses are caused by the increase of gaps and breaks. There was, however, no proof for a linear dependence of the percentage of aberrant mitoses on the increasing concentrations of the substances. The number of tetraploid mitoses, endoreduplications and hyperploid cells was within the normal range.Since in these investigations the number of chromosome exchanges was not increased, it can certainly be said that Primidone and Phenobarbital are not highly mutagenic substances.