Huovinen R L, Alanen K A, Collan Y U
Department of Oncology and Radiotherapy, University of Turku, Finland.
Acta Oncol. 1995;34(4):479-85. doi: 10.3109/02841869509094011.
Cell proliferation during antiestrogen toremifene treatment was studied using the DMBA-induced rat mammary carcinoma model. The volume corrected mitotic index (M/V INDEX) and the S-phase fraction (SPF) determined by flow cytometry (FCM) were used as proliferation markers. Two series of rats (A and B) treated with two dose levels of toremifene were used. The two series of tumors appeared to have different growth properties. In series A the tumors were rapidly growing with high proliferation rate. In this series, toremifene (3 mg/kg for 4 weeks) reduced significantly the mean MV/INDEX, but the slight reduction of the mean SPF was not significant. In series B the tumors grew slowly and had low levels of proliferation markers. One-third of the tumors were spontaneously stable in the untreated group. Higher dose of toremifene was used in this series (12 mg/kg for 4 weeks), and the number of regressing or stable tumors was 58% compared with 31% in series A. Taking into consideration the high number of spontaneously stable tumors in series B, it may be concluded that about one-third of the tumors regressed or remained stable due to toremifene treatment in both series. The reduction of the M/V INDEX was significant only when the regressing treated tumors were compared with the growing controls. The reduction of the SPF was not significant. We think that the M/V INDEX is a more appropriate method to measure cell proliferation than is the SPF in this tumor model, where the tumors are heterogenous and, e.g., spontaneous apoptosis is known to be frequent.
利用二甲基苯并蒽诱导的大鼠乳腺癌模型，研究了抗雌激素药物托瑞米芬治疗期间的细胞增殖情况。通过流式细胞术（FCM）测定的体积校正有丝分裂指数（M/V INDEX）和S期分数（SPF）被用作增殖标志物。使用了两组接受两种剂量水平托瑞米芬治疗的大鼠（A组和B组）。这两组肿瘤似乎具有不同的生长特性。在A组中，肿瘤生长迅速且增殖率高。在该组中，托瑞米芬（3mg/kg，持续4周）显著降低了平均MV/INDEX，但平均SPF的轻微降低并不显著。在B组中，肿瘤生长缓慢且增殖标志物水平较低。在未治疗组中，三分之一的肿瘤自发稳定。该组使用了更高剂量的托瑞米芬（12mg/kg，持续4周），与A组的31%相比，出现消退或稳定的肿瘤数量为58%。考虑到B组中自发稳定肿瘤的数量较多，可以得出结论，在两组中，约三分之一的肿瘤因托瑞米芬治疗而消退或保持稳定。仅当将接受治疗后消退的肿瘤与生长中的对照肿瘤进行比较时，M/V INDEX的降低才具有显著性。SPF的降低不显著。我们认为，在这个肿瘤模型中，M/V INDEX是一种比SPF更合适的测量细胞增殖的方法，因为该模型中的肿瘤是异质性的，例如已知自发凋亡很常见。
