Sensitivity to bleomycin and arabinoside cytosine in lymphocytes of patients affected by neuroblastoma and in those of their parents.

P Vernole, B Tedeschi, D Caporossi, B Nicoletti
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引用次数: 3

Abstract

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.

神经母细胞瘤患者及其父母淋巴细胞对博来霉素和阿拉伯糖胞嘧啶的敏感性。
染色体不稳定性在各种肿瘤患者中都有描述。我们之前报道了神经母细胞瘤患者及其父母淋巴细胞中阿霉素对脆弱部位诱导的高度敏感性。在寻找最合适的致裂剂以增强健康对照者和受肿瘤影响的患者之间可能的差异的过程中,我们现在测试了另外两种药物:博莱霉素,一种模拟辐射的药物,已经在体外用于受其他肿瘤影响的患者的染色体上;阿拉伯糖苷胞嘧啶,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都有高敏感性,但只有NB患者对阿拉伯糖胞嘧啶有高敏感性。此外,与健康对照组相比,这两种药物在患者及其父母的1p中诱导了更多的脆弱位点。我们在阿霉素治疗后已经观察到这种现象,可能与神经母细胞瘤细胞中1p的频繁缺失和异质性丧失有关。
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