CELL-PROLIFERATION IN DIMETHYLBENZ(A)ANTHRACENE(DMBA)-INDUCED RAT MAMMARY-CARCINOMA TREATED WITH ANTIESTROGEN TOREMIFENE

Cell proliferation during antiestrogen toremifene treatment was studie d using the DMBA-induced rat mammary carcinoma model, The volume corre cted mitotic index (M/V INDEX) and the S-phase fraction (SPF) determin ed by flow cytometry (FCM) were used as proliferation markers, Two ser ies of rats (A and B) treated with two dose levels of toremifene were used, The two series of tumors appeared to have different growth prope rties. In series A the tumors were rapidly growing with high prolifera tion rate, In this series, toremifene (3 mg/kg for 4 weeks) reduced si gnificantly the mean MV/INDEX, but the slight reduction of the mean SP F was not significant, In series B the tumors grew slowly and had low levels of proliferation markers, One-third of the tumors were spontane ously stable in the untreated group, Higher dose of toremifene was use d 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 co nsideration 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 reduct ion of the M/V INDEX was significant only when the regressing treated tumors were compared with the growing controls. The reduction of the S PF was not significant. We think that the M/V INDEX is a more appropri ate method to measure cell proliferation than is the SPF in this tumor model, where the tumors are heterogenous and, e.g., spontaneous apopt osis is known to be frequent.