Lambert E, Rees J K, Twentyman P R
Department of Clinical Oncology, University of Cambridge, UK.
Leukemia. 1992 Oct;6(10):1063-71.
We have used a 4-day MTT colorimetric assay to study drug sensitivity of leucocytes from leukaemia patients and from normal donors. Response to Adriamycin, vincristine, aclacinomycin A, 3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin (MX2), and melphalan has been determined, together with the effects of the resistance modifiers verapamil, cyclosporin A, and ethacrynic acid. Sensitivity of chronic lymphoblastic leukemia (CLL) lymphocytes to vincristine was much greater than that of normal lymphocytes or of leucocytes from myeloid leukaemia patients. These cells were also more sensitive to melphalan. Verapamil and cyclosporin A at clinically achievable doses of 1 microgram/ml produced significant chemosensitisation in normal and leukaemic specimens, but the sensitisation ratio was greater than or equal to 2 only in a minority of specimens, except in the case of sensitisation to vincristine seen in the majority of CLL specimens. Sensitisation was generally greater in the more chemo-resistant specimens. The ratio of sensitivities of cells to Adriamycin compared with aclacinomycin A was greatest in the more Adriamycin-resistant specimens which supports the idea that cross-resistance between these agents may not be great. This was not, however, true for the ratio of Adriamycin/MX2 sensitivity. Use of the MTT assay may allow the identification of patients who would benefit from treatment with resistance modifiers or with 'low-resistance' anthracyclines.
我们采用了为期4天的MTT比色法来研究白血病患者和正常供体白细胞的药物敏感性。已测定了对阿霉素、长春新碱、阿克拉霉素A、3'-脱氨基-3'-吗啉代-13-脱氧-10-羟基洋红霉素（MX2）和美法仑的反应，以及耐药修饰剂维拉帕米、环孢素A和依他尼酸的作用。慢性淋巴细胞白血病（CLL）淋巴细胞对长春新碱的敏感性远高于正常淋巴细胞或髓系白血病患者的白细胞。这些细胞对美法仑也更敏感。临床可达到的剂量为1微克/毫升的维拉帕米和环孢素A在正常和白血病标本中产生了显著的化学增敏作用，但仅在少数标本中增敏比大于或等于2，CLL标本中对长春新碱的增敏情况除外。在耐药性更强的标本中，增敏作用通常更大。在对阿霉素耐药性更强的标本中，细胞对阿霉素与阿克拉霉素A的敏感性之比最大，这支持了这些药物之间的交叉耐药性可能不大的观点。然而，阿霉素/MX2敏感性之比并非如此。使用MTT测定法可能有助于识别那些将从耐药修饰剂或“低耐药性”蒽环类药物治疗中获益的患者。
