Ince P, Finney K J, Appleton D R, Sunter J P, Watson A J
Br J Cancer. 1985 Oct;52(4):599-605. doi: 10.1038/bjc.1985.232.
A method is described enabling the direct measurement of vincristine resistance in intact tissues in vivo by morphological study. Using the metaphase arresting properties of the drug, counts were made of escaping anaphase and telophase mitotic figures at a range of doses. The proportion of post-metaphase mitotic figures is called the post-metaphase index (PMI). In 95 primary intestinal tumours induced by dimethylhydrazine (DMH) in rats, an increase in resistance to vincristine was shown over normal mucosa (P less than 0.001). The data were analysed by computer modelling and a linear relationship is demonstrated between the logit of the post-metaphase index, and log dose of vincristine. To achieve a PMI of 1% the fitted lines show an enhanced vincristine dose requirement over normal mucosa of 6 times in colonic tumours, and 8 times in small intestinal tumours. Non-neoplastic mucosa from the DMH-treated animals requires an enhanced dose of vincristine of 1.5 times, compared with normal mucosa, to achieve a PMI of 1%. Given current interest in the mechanism of vincristine resistance in cell lines this new approach provides a technique for assessing the resistance of solid tumours, both in vivo and in vitro, and for subsequent experimental manipulation.
本文描述了一种通过形态学研究在体内完整组织中直接测量长春新碱耐药性的方法。利用该药物的中期阻滞特性，在一系列剂量下对逸出的后期和末期有丝分裂图像进行计数。中期后有丝分裂图像的比例称为中期后指数（PMI）。在大鼠中由二甲基肼（DMH）诱导的95个原发性肠道肿瘤中，显示出对长春新碱的耐药性高于正常黏膜（P小于0.001）。通过计算机建模对数据进行分析，结果表明中期后指数的对数与长春新碱的对数剂量之间呈线性关系。为了达到1%的PMI，拟合线显示结肠肿瘤中长春新碱剂量需求比正常黏膜增加6倍，小肠肿瘤中增加8倍。与正常黏膜相比，DMH处理动物的非肿瘤性黏膜达到1%的PMI需要长春新碱剂量增加1.5倍。鉴于目前对细胞系中长春新碱耐药机制的关注，这种新方法提供了一种在体内和体外评估实体瘤耐药性以及后续实验操作的技术。
