Rl. Huovinen et al., CELL-PROLIFERATION IN DIMETHYLBENZ(A)ANTHRACENE(DMBA)-INDUCED RAT MAMMARY-CARCINOMA TREATED WITH ANTIESTROGEN TOREMIFENE, Acta oncologica, 34(4), 1995, pp. 479-485
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.