Repair of DNA following incorporation of 1-beta-D-arabinofuranosylcytosine into herpes simplex virus type 1.
The nucleoside analogue 1-beta-D-arabinofuranosylcytosine (ara-C) is incorporated into herpes simplex virus type 1 (HSV-1) DNA, and this correlates with inhibition of virus replication. The technique of Weigle-type reactivation (WR) was used to compare the ability of induced cellular DNA repair pathways to recognize or repair ara-C incorporated into HSV-1 DNA and ultraviolet (UV)-irradiated virus DNA (254 nm). Pretreatment of monkey cells with low-fluence UV irradiation, growth in cis-dichlorodiammineplatinum(II), or growth in ara-C followed by infection after a 24-hr incubation period resulted in enhanced survival of UV-irradiated HSV-1. Under the same experimental conditions, no reactivation of HSV-1 inactivated by growth in ara-C is observed. Comparisons between uninfected Vero cells exposed to UV irradiation (30 J/m2) or grown in 10(-6) M ara-C demonstrated repair replication in irradiated cells, whereas there was no evidence for DNA repair at various time intervals following removal of the nucleoside analogue. These observations suggest that, once ara-C is incorporated into HSV-1 or eukaryotic DNA, it is not recognized as a repairable lesion within the limits of the DNA repair assays used in these studies.
D000818:Animals; D002460:Cell Line; D002522:Chlorocebus aethiops; D002945:Cisplatin / Q000633:toxicity; D003561:Cytarabine / Q000378:metabolism* / Q000633:toxicity; D004260:DNA Repair; D004261:DNA Replication / Q000187:drug effects; D004279:DNA, Viral / Q000235:genetics* / Q000302:isolation & purification; D007668:Kidney; D018139:Simplexvirus / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D014466:Ultraviolet Rays
D004279:DNA, Viral; D003561:Cytarabine; D002945:Cisplatin