Mutagenesis at putative apurinic sites in alkylated single-stranded DNA of parvovirus H-1 propagated in human cells.
The treatment of parvovirus H-1, a single-stranded DNA virus, with ethylnitrosourea immediately prior to infection of human cells, resulted in both virus mutagenesis and lethality (immediate hits). The incubation of treated virus, prior to inoculation, under conditions promoting the release of alkylated bases, slightly reduced the mutagenicity of ethylnitrosourea but significantly increased its killing effect (delayed hits). In untreated cells, the appearance of one apurinic/apyrimidinic site in viral DNA correlated with the formation of approximately one delayed lethal hit per virus. Cells which had been sublethally UV irradiated prior to infection, were able to overcome about 20% of the delayed lethal hits inflicted to ethylnitrosourea-treated H-1. This UV-enhanced reactivation was accompanied by viral mutagenesis and was not observed for immediate lethal hits. Therefore, UV irradiation of human cells appears to trigger a conditioned recovery response which might alleviate a block to the replication of single-stranded DNA containing apurinic sites, allowing these noncoding lesions to direct mutagenesis. UV-irradiated cells also displayed a mutator phenotype towards untreated parvovirus H-1. In contrast, ethylnitrosourea failed to induce human cells to cause mutagenesis of undamaged viral DNA, although it enhanced their ability to reactivate damaged virus.
D000478:Alkylation; D002460:Cell Line; D004260:DNA Repair; D004261:DNA Replication / Q000528:radiation effects; D004277:DNA, Single-Stranded / Q000235:genetics*; D004279:DNA, Viral / Q000235:genetics*; D005038:Ethylnitrosourea; D006801:Humans; D009154:Mutation; D010321:Parvoviridae / Q000235:genetics*; D014466:Ultraviolet Rays; D014779:Virus Replication / Q000528:radiation effects
D004277:DNA, Single-Stranded; D004279:DNA, Viral; D005038:Ethylnitrosourea