GENOTOXICITY OF PURINE ACYCLIC NUCLEOTIDE ANALOGS

The genotoxic and embryotoxic effects of phosphonomethoxyalkylpurines, a new group of antiviral agents, decrease in the following order: PME G > PMEthioG > PMEDAP > PMEA > (R)-PMPDAP = (R)-PMPA. Results of the p resent study are fully consistent with the previously found efficacy o f their diphosphates to inhibit the replicative DNA polymerases. The m arked genotoxicity of PMEG and PMEthioG is comparable to that of mitom ycin C, whereas the moderate genotoxicity of PMEA is comparable to tha t of AZT. (R)-PMPDAP and (R)-PMPA did not induce any structural aberra tions of chromosomes under the experimental conditions.