Nagourney R A, Evans S S, Messenger J C, Su Y Z, Weisenthal L M
Memorial Cancer Institute, Long Beach, California 90806.
Br J Cancer. 1993 Jan;67(1):10-4. doi: 10.1038/bjc.1993.3.
2-Chlorodeoxyadenosine (2-CDA) is an adenosine deaminase resistant analogue of deoxyadenosine which has shown clinical activity in human hematologic neoplasms. The exact mode of action of this drug remains the subject of investigation. We applied the Differential Staining Cytotoxicity (DiSC) assay to 50 human tumour specimens obtained from patients with a variety of hematologic malignancies to characterise the activity spectrum of 2-CDA. We evaluated the disease-specific activity of this agent in vitro and compared its relative cytotoxicity with that of other antineoplastic agents in current clinical use. Comparisons were conducted against nitrogen mustard, doxorubicin, vincristine and cytosine arabinoside. Our results indicate that 2-CDA has activity in myeloid and many lymphoid neoplasms but that multiple myeloma specimens reveal significant resistance. Cross resistance studies reveal a correlation between 2-CDA and the alkylator nitrogen mustard but no correlation between 2-CDA and doxorubicin, vincristine nor cytosine arabinoside. The results suggest 2-CDA activity in many human hematologic neoplasms with the clear exception of multiple myeloma and further suggest a relationship between this agent and alkylators of the mustard class. The DiSC assay may provide useful insights in the pre-clinical evaluation of new antineoplastic drugs and may help to elucidate drug activities and mechanisms of action.
2-氯脱氧腺苷（2-CDA）是脱氧腺苷的一种抗腺苷脱氨酶类似物，已在人类血液肿瘤中显示出临床活性。这种药物的确切作用方式仍在研究中。我们将差异染色细胞毒性（DiSC）试验应用于从患有各种血液系统恶性肿瘤的患者身上获取的50份人类肿瘤标本，以表征2-CDA的活性谱。我们在体外评估了该药物的疾病特异性活性，并将其相对细胞毒性与目前临床使用的其他抗肿瘤药物进行了比较。与氮芥、阿霉素、长春新碱和阿糖胞苷进行了比较。我们的结果表明，2-CDA在髓系和许多淋巴系肿瘤中具有活性，但多发性骨髓瘤标本显示出明显的耐药性。交叉耐药性研究表明，2-CDA与烷化剂氮芥之间存在相关性，但2-CDA与阿霉素、长春新碱或阿糖胞苷之间不存在相关性。结果表明，2-CDA在许多人类血液肿瘤中具有活性，但多发性骨髓瘤明显除外，进一步表明该药物与芥子类烷化剂之间存在关系。DiSC试验可能为新抗肿瘤药物的临床前评估提供有用的见解，并可能有助于阐明药物活性和作用机制。
