Elli R, Chessa L, Antonelli A, Petrinelli P, Ambra R, Marcucci L
Dipartimento di Biopatologia Umana, Università La Sapienza, Rome, Italy.
Cancer Genet Cytogenet. 1996 Apr;87(2):112-6. doi: 10.1016/0165-4608(95)00294-4.
DNA topoisomerase II is involved in DNA topologic changes through the formation of a cleavable complex. This is stabilized by the antitumor drug VP16, which results in DNA breakage, aberrant recombination, and cell death. In this work, we compare the chromosomal damage induced by VP16 with that induced by bleomycin (BLM) in lymphoblasts from patients affected by the chromosome breakage syndromes ataxia telangiectasia (AT), xeroderma pigmentosum (XP), and Bloom syndrome (BS), and by the progeroid syndromes Werner (WS) and Cockayne (CS). Patients affected by AT, XP, BS, and WS have a greatly enhanced risk of developing cancer. The results show that AF and WS cells are hypersensitive to VP16, as revealed in the higher proportion of metaphases showing exchange figures and more than two breaks. All lines except AT and one CS line showed normal sensitivity to BLM. Our data on the sensitivity to VP16 of all these mutant cells underline the fact that VP16 damage is amplified only in cells that have abnormal illegitimate recombination (i.e., AT and WS).
DNA拓扑异构酶II通过形成可裂解复合物参与DNA拓扑结构的改变。抗肿瘤药物VP16可使这种复合物稳定，进而导致DNA断裂、异常重组和细胞死亡。在本研究中，我们比较了VP16与博来霉素（BLM）在患有染色体断裂综合征（共济失调毛细血管扩张症（AT）、着色性干皮病（XP）和布卢姆综合征（BS））以及早衰综合征（沃纳综合征（WS）和科凯恩综合征（CS））患者的淋巴母细胞中诱导的染色体损伤。患有AT、XP、BS和WS的患者患癌风险大大增加。结果表明，AF和WS细胞对VP16高度敏感，表现为中期相中出现交换图形和超过两个断裂的比例更高。除AT和一个CS细胞系外，所有细胞系对BLM均表现出正常敏感性。我们关于所有这些突变细胞对VP16敏感性的数据强调了这样一个事实，即VP16损伤仅在具有异常非同源重组的细胞（即AT和WS）中被放大。
