Potent antiviral 2'-fluoro-arabinosyl pyrimidine nucleosides: lack of mutagenic activity.
The carcinogenicity of many drugs, such as antitumor agents, is a subject of growing concern. The newly developed pyrimidine nucleosides, 2'-fluoro-5-iodo-1-beta-D-arabinofuranosylcytosine (FIAC) and 2'-fluoro-1-beta-D-arabinofuranosyl-5-methyluracil (FMAU), have shown potent anti-herpes virus activity in tissue cultures, laboratory animals and man and an activity to inhibit the growth of certain tumor cell lines in vitro. Radioactivity of 14C-labeled FIAC and FMAU is incorporated into the DNA of normal and neoplastic mammalian tissues. However, we now report that FIAC and FMAU are inactive in a bacterial mutagenesis assay (Salmonella-microsome test) and in a mammalian cell mutagenesis assay employing V79 Chinese hamster cells in vitro. Both agents did not induce unscheduled DNA synthesis in primary Wistar rat hepatocytes in vitro.
D000818:Animals; D000998:Antiviral Agents; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives* / Q000633:toxicity; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003561:Cytarabine / Q000031:analogs & derivatives* / Q000633:toxicity; D004247:DNA / Q000096:biosynthesis; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D009152:Mutagenicity Tests; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects / Q000235:genetics; D014529:Uridine / Q000031:analogs & derivatives*
D000998:Antiviral Agents; D003561:Cytarabine; D001086:Arabinofuranosyluracil; C026023:fiacitabine; D004247:DNA; C034935:clevudine; D014529:Uridine