Potentiation of ribavirin-induced teratogenesis by natural purines

Abstract

Ribavirin, a nucleoside analog, has been shown to possess much promise as an effective antiviral and antitumor agent. In addition, ribavirin has been reported to have significant, reproducible teratogenic activity (Kilham and Ferm, 1977). As the teratogenic effects of certain nucleoside analogs have been found to be altered by natural nucleic acid bases, it was of interest to investigate ribavirin's teratogenic properties in this light. The experiments reported here evaluated the effects of simultaneous administrations of ribavirin and purine nucleic acid bases on developing hamster embryos. The injection of ribavirin-adenine and/or ribavirin-guanine on Day 8 of gestation was observed to significantly increase the percentage of resorbed implantation sites and the percentage of malformed hamster fetuses as compared with the administration of an equivalent dose of ribavirin alone. The anomalies in the hamster fetuses produced by the administration of ribavirin-purine combinations were observed to be generally more severe than anomalies in those fetuses exposed to an equivalent amount of ribavirin alone.