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 in human peripheral blood lymphocytes (PBLs) were evaluated.Treatment of HCMV-infected PBLs with camptothecin (0.05 to 0.3 μg/ml),an inhibitor of topoisomerase Ⅰ,for 30 hr resulted in a significant (P<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 μg/ml),an inhibitor of poly (ADP-ribose) polymerase,or novobiocin (3 to 30 μg/ml) an inhibitor of topoisomerase Ⅱ or excision repair processes for 30 hr.Chromatid-type breaks including chromosome 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.Furthermors,these findings suggest that HCMV infection does not inflict direct DNA damage which is repaired through 3-AB-or novobiecinsensitive pathways.