Analysis of toxic and mutagenic activities of antiherpesvirus nucleosides against HeLa cells and herpes simplex virus type 1.
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.
Suzutani
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Department of Microbiology, Asahikawa Medical College, Japan.
Machida
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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
D000998:Antiviral Agents; D009153:Mutagens; D009705:Nucleosides; C020235:brivudine; D001086:Arabinofuranosyluracil; C031368:sorivudine; D014740:Vidarabine; D001973:Bromodeoxyuridine; D000212:Acyclovir