title: Analysis of toxic and mutagenic activities of antiherpesvirus nucleosides against HeLa cells and herpes simplex virus type 1.
abstract: The toxic and mutagenic activities of five antiherpesvirus agents to HeLa cells and herpes simplex virus type 1 (HSV-1) were investigated. 5-Iodo-2'-deoxyuridine (IDU) and 9-beta-D-arabinofuranosyl-adenine (araA) showed very potent inhibitory effects on cell growth and the cloning efficiency of HeLa cells, whereas 1-beta-D-arabinofuranosyl-E-5-(2-bromovinyl)uracil (BV-araU), E-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and 9-(2-hydroxyethoxymethyl)guanine (ACV) showed less inhibitory effect. 50% inhibitory doses of BV-araU and BVDU for cell growth were 657 and 253 micrograms/ml, respectively. Although the growth inhibitory activity of BVDU was very weak, as above, the mutagenic activity of this drug to the cells, estimated by induction of colchicine-resistant mutants, was observed to be 4 micrograms/ml, which was a markedly smaller dose than the inhibitory dose for cell growth, and the highest frequency of mutation of the cells was shown at 100 micrograms/ml of BVDU. This activity was more potent than that of IDU. No mutagenic activity of BV-araU, araA and ACV to cells was observed within the concentration range of 1-800 micrograms/ml. IDU showed high mutagenic activity to HSV-1 growing in human embryo lung fibroblasts, and IDU-resistant mutants were induced at a high frequency. BVDU also induced a small amount of BVDU-resistant mutant virus, although this drug induced many mutant cells. No mutagenic activity of BV-araU, araA and ACV to HSV-1 was observed.
authors.affiliation: Department of Microbiology, Asahikawa Medical College, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Suzutani
authors.forename: H
authors.initials: H
authors.lastname: Machida
mesh_terms: D000212:Acyclovir / Q000633:toxicity; D000998:Antiviral Agents / Q000633:toxicity*; D001086:Arabinofuranosyluracil / Q000031:analogs & derivatives / Q000633:toxicity; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives / Q000633:toxicity; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D009153:Mutagens; D009705:Nucleosides / Q000633:toxicity*; D018139:Simplexvirus / Q000235:genetics*; D014740:Vidarabine / Q000633:toxicity; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D009153:Mutagens; D009705:Nucleosides; C020235:brivudine; D001086:Arabinofuranosyluracil; C031368:sorivudine; D014740:Vidarabine; D001973:Bromodeoxyuridine; D000212:Acyclovir