The effect of (E)-5-(2-bromovinyl)-2'-deoxyuridine on DNA repair and mutagenesis of herpes simplex virus type 1.
Growth of HSV-1 in (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) results in incorporation of the analog into HSV-1 DNA. Employing the technique of Weigle-type reactivation (WR), HSV-1 inactivated by uv irradiation but not by growth in BVDU is a substrate for induced cellular repair pathways. Growth of mammalian cells in BVDU does not induce cellular repair pathways detected by WR. HSV-1 temperature sensitive (ts) mutants demonstrate an increased reversion frequency to the nonpermissive phenotype (ts+) following growth in a high concentration of BVDU. A ts mutant did not display an increased reversion frequency following growth in equally inhibitory concentrations of an HSV-1 polymerase inhibitor, aphidicolin. These findings suggest that BVDU incorporated into HSV-1 DNA may not be readily excised and may be a mutagenic lesion in viral DNA, although other explanations are possible.
Bubley
G J
GJ
Charles A. Dana Research Institute, Boston, Massachusetts.
Balzarini
J
J
Crumpacker
C S
CS
de Clercq
E
E
Schnipper
L E
LE
D000818:Animals; D001973:Bromodeoxyuridine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D004260:DNA Repair / Q000187:drug effects*; D004279:DNA, Viral / Q000187:drug effects* / Q000378:metabolism; D005814:Genes, Viral; D009154:Mutation; D018139:Simplexvirus / Q000187:drug effects / Q000235:genetics* / Q000254:growth & development / Q000528:radiation effects; D014466:Ultraviolet Rays; D014709:Vero Cells
D004279:DNA, Viral; C020235:brivudine; D001973:Bromodeoxyuridine