Ln. Salling et al., THE EFFECT OF CASTRATION ON TUMOR-GROWTH RATE AND CELL-KINETICS IN HORMONE-SENSITIVE AND HORMONE INSENSITIVE RAT PROSTATIC ADENOCARCINOMAS, Scandinavian journal of urology and nephrology, 1995, pp. 73-79
Cell kinetics were measured in vivo in four experimental rat prostatic
adenocarcinomas grown in normal or castrated rats. The aim was to inv
estigate the effect of castration on growth rate and cell kinetics in
hormone sensitive and hormone insensitive prostatic carcinomas. We use
d two anaplastic, hormone insensitive, fast growing tumors (Dunning R-
3327-AT1 H and E), as well as two well differentiated, hormone sensiti
ve, slow growing tumors (R-3327-H and R-3327-PAP). DNA ploidy, S-phase
transit time (T-s), the labeling index (LI) and potential doubling ti
me (T-pot) was determined by dual parameter flow cytometry, after in v
ivo labeling, using bromodeoxyuridine (BUdR) and the tumor doubling ti
me (DT) was determined from growth curves. After castration DT in the
hormone sensitive H-subline changed from 21,7 days to 82,0 days, and i
n the PAP-subline from 22,2 days to 33,2 days. No significant changes
in T-pot were observed. In the anaplastic tumors no differences in nei
ther DT nor T-pot were seen. The cell loss factor (CLF) was relatively
low in the two anaplastic tumors (0.55-0.59) compared to the well dif
ferentiated tumors. The CLF was unaffected by castration in the poorly
differentiated tumors, whereas it increased significantly (from 0.75
to 0.92, P=0.005) after castration in the H-tumor, and showed a non-si
gnificant increase in the PAP-tumor. This implies that the decrease in
tumor growth in the hormone sensitive tumors is due to an increase in
cell death, not a decrease in cell proliferation. These data indicate
that CLF is the dominating factor in the reduced growth following and
rogen ablation in an androgen sensitive tumor. This study suggests tha
t T-pot might be and additional predictor of a tumors proliferating ra
te and it may provide important information of the human prostatic can
cer.