Natarajan A T, van Zeeland A A, Zwanenburg T S
Princess Takamatsu Symp. 1983;13:227-42.
The influence of inhibitors of poly(ADP-ribose) polymerase such as 3-aminobenzamide (3AB) and benzamide (B) on the spontaneously occurring as well as mutagen induced chromosomal aberrations, sister chromatid exchanges (SCEs) and point mutations has been studied. In addition, we have measured the influence of 3AB on DNA repair following treatment with physical and chemical mutagens. Post treatment of X-irradiated mammalian cells with 3AB increases the frequencies of induced chromosomal aberrations by a factor of 2 to 3. Both acentric fragments and exchanges increase indicating that the presence of 3AB slows down the repair of DNA strand breaks (probably DNA double strand breaks), thus making breaks available for interaction with each other to give rise to exchanges. 3AB, when present in the medium containing bromodeoxyuridine(BrdUrd) during two cell cycles, increases the frequencies of SCEs in Chinese hamster ovary cells (CHO) in a concentration dependent manner leading to about a 10-fold increase at 10 mM concentration. Most 3AB induced SCEs occur during the second cell cycle, in which DNA containing bromouridine (BU) is used as template for replication. BU containing DNA appears to be prone to errors during replication. The extent of increase in the frequencies of SCEs by 3AB is correlated with the amount of BU incorporated in the DNA of the cells. The frequencies of spontaneously occurring DNA single strand breaks in cells grown in BrdUrd containing medium are higher than in the cells grown in normal medium and this increase depends on the amount of BU incorporated in the DNA of these cells. We have studied the extent of increase in the frequencies of SCEs due to 1 mM 3AB in several human cell lines, including those derived from patients suffering from genetic diseases such as ataxia telangiectasia (A-T), Fanconi's anemia (FA), and Huntington's chorea. None of these syndromes showed any increased response when compared to normal cells. 3AB, however, increased the frequencies of spontaneously occurring chromosomal aberrations in A-T and FA cells. 3AB does not influence the frequencies of SCEs induced by UV or mitomycin C (MMC) in CHO cells. However, it increases the frequencies of SCEs induced by ethyl methanesulfonate (EMS) and methyl methanesulfonate (MMS). Under the conditions in which 3AB increases the frequencies of spontaneously occurring as well as induced SCEs, it does not increase the frequencies of point mutations in hypoxanthine-guanine phosphoribosyltransferase (HGPRT) locus. 3AB does not influence the amount of repair replication following dimethylsulphate (DMS) treatment of human fibroblasts, or UV irradiated human lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
已经研究了聚（ADP - 核糖）聚合酶抑制剂如3 - 氨基苯甲酰胺（3AB）和苯甲酰胺（B）对自发发生的以及诱变剂诱导的染色体畸变、姐妹染色单体交换（SCE）和点突变的影响。此外，我们还测量了3AB对物理和化学诱变剂处理后DNA修复的影响。用3AB对经X射线照射的哺乳动物细胞进行后处理，可使诱导的染色体畸变频率增加2至3倍。无着丝粒片段和交换均增加，这表明3AB的存在减缓了DNA链断裂（可能是DNA双链断裂）的修复，从而使断裂能够相互作用产生交换。当3AB在两个细胞周期中存在于含有溴脱氧尿苷（BrdUrd）的培养基中时，它以浓度依赖方式增加中国仓鼠卵巢细胞（CHO）中SCE的频率，在10 mM浓度下导致增加约10倍。大多数3AB诱导的SCE发生在第二个细胞周期，其中含有溴尿苷（BU）的DNA用作复制模板。含有BU的DNA在复制过程中似乎容易出错。3AB使SCE频率增加的程度与细胞DNA中掺入的BU量相关。在含有BrdUrd的培养基中生长的细胞中，自发发生的DNA单链断裂频率高于在正常培养基中生长的细胞，并且这种增加取决于这些细胞DNA中掺入的BU量。我们研究了在几种人类细胞系中，包括来自患有遗传性疾病如共济失调毛细血管扩张症（A - T）、范可尼贫血（FA）和亨廷顿舞蹈症患者的细胞系中，1 mM 3AB导致的SCE频率增加程度。与正常细胞相比，这些综合征均未显示出任何增加的反应。然而，3AB增加了A - T和FA细胞中自发发生的染色体畸变频率。3AB不影响UV或丝裂霉素C（MMC）在CHO细胞中诱导的SCE频率。然而，它增加了甲磺酸乙酯（EMS）和甲磺酸甲酯（MMS）诱导的SCE频率。在3AB增加自发发生的以及诱导的SCE频率的条件下，它不会增加次黄嘌呤 - 鸟嘌呤磷酸核糖转移酶（HGPRT）位点的点突变频率。3AB不影响硫酸二甲酯（DMS）处理人类成纤维细胞或UV照射人类淋巴细胞后的修复复制量。（摘要截取自400字）
