摘要
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. Trealment of HCMV-infected PBLs with camptothecin (0.05 to 0.3μg/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 30μg/ml), an inhibitor of poly (ADP-ribose) poiymerase, ur novobiocin 3 to 30 |ig/ml) an inhibitor of topoiso-merase I 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. Furthermore, these findings suggest that HCMV infection does rol inflict dircc: DNA damage which is repaired through 3-AB- or novobiocinsensitive pathways.Human cytomegalovirus (HCMV) is a common pathogen which irferfs about 80% of the world's population causing, for the most part, persistent subcliniclil infeclions (Wellcr, 1971). A relatively small percentage of otherwise healthy immunologically competent people experience clinical HCMV disease (Cohen et al., 1985). Generalized HCMV infection, however, is the bane of individuals whose immune system is compromised (Schooley, 1990) Rubin, 1990). Molecular epidemiological studies strongly suggest that HCMV is one of the most frequent cause of congenital infections and that these infections result in a high incidence of birth defects and developmental abnormalities (Alford et al., 1990). Several studies (Nachtigal et al., 1978; Luleci et al., 1980; AbuBakar et al., 1988) have shown that HCMV infectior can result in an increase in the frequency of chromosome aberrations. Since the ability to cause chromosome damage may be significant in the induction of birth defects and possibly in HCMV-induced malignancy, we undertook the present investigation to evaluate the mechanisms by which HCMV may cause chromosome damage. In ths study, the effects of selected DNA repair inhibitors on the frequency of HCMV-induced chromosome aberrations were evaluated. The results indicae that the presence of camptothecin, but nut 3-aminobenzamidc (3-AB) ro novobiocin, results in a concentration-dependent increase in the frequent) of chromosome aberrations in HCMV-infected peripheral blood lymphocytes (PBLs). Accordingly, it is proposed that HCMV-induced chromosome damage in PBLs does not substantially involve DNA repair activities sensitive to inhibition of poly ADP-ribosylation or excision repair processes, but is related to camp of thccin-sersitive DNA repair, conceivably involving the activity of topoisomrrasc I .
本文评价了所选用的DNA修复抑制剂对人类巨细胞病毒(HCMV)诱发外周血淋巴细胞(PBLs)染色体畸变频率的影响。以拓扑酶Ⅰ的一种抑制剂——喜树碱(0.05—0.3μg/m1)处理HCMV感染的人类PBLs30小时,结果导致HCMV诱发的染色体损伤频率显著的协同性增加(P<0.O1)。另一方面以ADP核糖聚合酶的一种抑制剂——3—氨基苯酰胺(3—AB)(3—30μg/ml),或者拓扑酶Ⅱ的一种抑制剂——新霉素(3—30μg/ml)处理HCMV感染的PBLs30时小,染色体损伤频率未见明显增加。在喜树碱处理的HCMV感染细胞中,染色单体型断裂包括染色体交换是染色体畸变的主要类型,这提示HCMV感染与单链NDA断裂有关,这些发现还提示,HCMV感染不会造成通过3-AB或新霉素敏感途径修复的直接DNA损伤。
