Comparison of human versus Syrian hamster cells in culture for induction of mitotic inhibition, binucleation and multinucleation, following treatment with four aneuploidogens.
The responses of human and rodent cells in vitro to aneuploidy-inducing chemicals were compared. Normal human fibroblasts and Syrian hamster embryo fibroblasts were treated with four aneuploidogens; Colcemid, vincristine, and the oestrogens diethylstilboestrol and oestra-1,3,5(10)-triene-3,17beta-diol (17beta-oestradiol). All compounds at a critical dose inhibited cell growth of both cell types. The concentrations of the two oestrogens required to inhibit growth of human and hamster cells were similar, whereas for the two mitotic inhibitors Colcemid and vincristine, the concentrations required for growth-inhibitory effects were lower for human cells than for hamster cells. The growth inhibition was reversible for all treatments except Colcemid. Doses that inhibited cell growth also resulted in large numbers of mitotic cells appearing in a time-dependent manner, indicating that both cell types were arrested in mitosis by all four compounds. The time required for maximum increases in the mitotic indices was greater for human cells, which is consistent with the longer cell cycle of these cells in culture. Few binucleated cells of either type were induced by any treatment except 17beta-oestradiol, which induced a high level of binucleated hamster cells, but not human cells. With time, the mitotic index of all treated cells decreased. For hamster cells, this was always accompanied by a large increase in multinucleated cells. The percentage of multinucleated hamster cells reached 50-60% in the Colcemid- and vincristine-treated cultures and 30-35% in the oestrogen-treated cultures. In contrast, the level of multinucleated human cells was significantly lower for all treatments. Colcemid and vincristine treatments induced 20-25% multinucleated human cells, and the oestrogens induced <5% multinucleated human cells. This latter finding appears to be the most significant difference between the two cell types. These results indicate that human cells respond differently from rodent cells to agents that induce mitotic arrest. This may help in understanding the decreased induction of aneuploidy in human cells by these compounds.
Tsutsui
T
T
Department of Pharmacology, School of Dentistry at Tokyo, The Nippon Dental University, Tokyo 102, Japan.
Suzuki
N
N
Maizumi
H
H
Barrett
J C
JC