Potent anti-viral 5-(2-bromovinyl) uracil nucleosides are inactive at inducing gene mutations in Salmonella typhimurium and V79 Chinese hamster cells and unscheduled DNA synthesis in primary rat hepatocytes.
(E)-5-(2-bromovinyl)-2'-deoxyuridine (BDVU), one of the most potent and selective anti-herpes agents described to date, and its close congeners (E)-5-(2-bromovinyl)-1-beta-D-arabinofuranosyluracil (BVaraU) and (E)-5-(2-bromovinyl)uracil (BVU), as well as the reference compounds 5-iodo-2'-deoxyuridine (IDU) and 5-trifluoro-2'-deoxythymidine (TFT) were examined for their genotoxic potential. With the exception of a weak activity of TFT in the newly developed strain TA 102, none of the compounds was active in a bacterial cell mutagenesis (Salmonella/microsome) assay. Nor did they induce DNA repair (unscheduled DNA synthesis) in primary rat hepatocytes. In a mammalian cell mutagenesis assay using V79 Chinese hamster cells, the reference compounds IDU and TFT proved highly cytotoxic and mutagenic, whereas BVDU, BVaraU and BVU were neither cytotoxic nor mutagenic.
D000818:Animals; D000998:Antiviral Agents / Q000633:toxicity*; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives / Q000633:toxicity; D001976:Bromouracil / Q000031:analogs & derivatives* / Q000633:toxicity; D002478:Cells, Cultured; D006224:Cricetinae; D003412:Cricetulus; D004260:DNA Repair / Q000187:drug effects*; D008099:Liver / Q000378:metabolism*; D008297:Male; D009153:Mutagens; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects
D000998:Antiviral Agents; D009153:Mutagens; C020235:brivudine; D001976:Bromouracil; C046140:5-(2-bromovinyl)uracil; D001973:Bromodeoxyuridine