Vernole P, Tedeschi B, Caporossi D, Nicoletti B
Dept. Public Health & Cell Biology, II University of Rome, Tor Vergata, Italia.
Cancer Biother. 1993 Spring;8(1):87-94. doi: 10.1089/cbr.1993.8.87.
Chromosomal instability has been described in patients affected by various tumors. We previously reported a high sensitivity to fragile sites induction by aphidicolin in lymphocytes from patients affected by neuroblastoma and in those from their parents. In the search for the most suitable clastogenic agent to enhance the possible differences between healthy controls and patients affected by tumors, we have now tested two other drugs: bleomycin, a radiomimetic agent already used in vitro on chromosomes of patients affected by other tumors and arabinoside cytosine, an inhibitor of DNA polymerases alfa and beta. We observed a high sensitivity to bleomycin both in patients and in their parents, but to arabinoside cytosine only in NB patients. Moreover, the two drugs induced more fragile sites in 1p in patients and in their parents than in healthy controls. This phenomenon, which we already observed after treatment with aphidicolin, might be related to the frequent deletions and loss of heterozigosity in 1p in neuroblastoma cells.
染色体不稳定已在患有各种肿瘤的患者中被描述。我们之前报道过，受神经母细胞瘤影响的患者及其父母的淋巴细胞对阿非迪霉素诱导的脆性位点高度敏感。为了寻找最合适的致断裂剂以增强健康对照与肿瘤患者之间可能存在的差异，我们现在测试了另外两种药物：博来霉素，一种已在体外用于其他肿瘤患者染色体的放射模拟剂；以及阿糖胞苷，一种DNA聚合酶α和β的抑制剂。我们观察到患者及其父母对博来霉素均高度敏感，但仅神经母细胞瘤患者对阿糖胞苷敏感。此外，这两种药物在患者及其父母中诱导出的1p脆性位点比健康对照更多。这种我们在用阿非迪霉素治疗后就已观察到的现象，可能与神经母细胞瘤细胞中1p频繁的缺失和杂合性丧失有关。
