Modulation of the frequency of human cytomegalovirus-induced chromosome aberrations by camptothecin.
The effects of selected DNA repair inhibitors on the frequency of human cytomegalovirus (HCMV)-induced chromosome aberrations were evaluated in human peripheral blood lymphocytes (PBLs). Treatment of HCMV-infected PBLs with camptothecin (0.05 to 0.3 micrograms/ml), an inhibitor of topoisomerase I, for 30 hr resulted in a significant (P less than 0.01) synergistic enhancement of the frequency of HCMV-induced chromosome damage. On the other hand, a significant increase in the frequency of chromosome damage was not noted for infected PBLs treated with either 3-aminobenzamide (3-AB; 3 to 30 micrograms/ml), an inhibitor of poly(ADP-ribose) polymerase, or novobiocin (3 to 30 micrograms/ml), an inhibitor of topoisomerase II or excision repair processes, for 30 hr. Chromatid-type breaks and exchanges were the predominant type of chromosome aberrations observed in the HCMV-infected cells treated with camptothecin, suggesting that HCMV infection is associated with the induction of single-strand DNA breaks. Furthermore, these findings suggest that HCMV infection does not inflict direct DNA damage which is repaired through 3-AB- or novobiocin-sensitive pathways.
Deng
C Z
CZ
Department of Microbiology, University of Texas Medical Branch, Galveston 77550.
AbuBakar
S
S
Fons
M P
MP
Boldogh
I
I
Albrecht
T
T
D001549:Benzamides / Q000494:pharmacology; D002166:Camptothecin / Q000494:pharmacology*; D002478:Cells, Cultured; D002869:Chromosome Aberrations / Q000502:physiology*; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000382:microbiology; D009675:Novobiocin / Q000494:pharmacology; D000067856:Poly(ADP-ribose) Polymerase Inhibitors
D001549:Benzamides; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D009675:Novobiocin; C025160:3-aminobenzamide; D002166:Camptothecin