Aneuploidy induction in human fibroblasts: comparison with results in Syrian hamster fibroblasts.
The susceptibility of human fibroblast cells in culture to neoplastic transformation by chemical carcinogens is appreciably lower than that of rodent fibroblasts. We have proposed that a key step in the neoplastic progression of Syrian hamster embryo fibroblasts is the induction of aneuploidy by carcinogens. It is possible that the different sensitivity to neoplastic transformation of Syrian hamster versus human cells is due to a difference in genetic stability following treatment with chemicals inducing aneuploidy. Therefore, we measured the induction of numerical chromosome changes in normal human fibroblasts and Syrian hamster fibroblasts by 4 specific aneuploidogens. Dose- and time-dependent studies were performed. Nondisjunction, resulting in aneuploid cells with a near-diploid chromosome number, in up to 14-28% of the hamster cells was induced by colcemid (0.1 microgram/ml), vincristine (30 ng/ml), diethylstilbestrol (DES) (1 microgram/ml) or 17 beta-estradiol (10 micrograms/ml). In contrast, human cells displayed far fewer aneuploid (near-diploid) cells, i.e., 8% following treatment with colcemid (0.02 micrograms/ml) or vincristine (10 ng/ml) and only 3% following treatment with DES (6 micrograms/ml) or 17 beta-estradiol (20 micrograms/ml). The doses at which the maximum effect was observed are given. Treatment of human cells induced a higher incidence of cells with a near-tetraploid chromosome number, which was similar to the level observed in treated hamster cells except at the highest doses. These results indicate that human cells respond differently from hamster cells to agents that induce aneuploidy. In particular, nondisjunction yielding aneuploid human fibroblasts with a near-diploid chromosome number was less frequent. The magnitude of the observed species differences varied with different chemicals. The difference in aneuploidy induction may contribute, in part, to species differences in susceptibility of fibroblasts to neoplastic transformation.
Tsutsui
T
T
Department of Pharmacology, School of Dentistry, Tokyo, Japan.
Suzuki
N
N
Maizumi
H
H
Barrett
J C
JC
D000782:Aneuploidy; D000818:Animals; D002478:Cells, Cultured; D006224:Cricetinae; D003703:Demecolcine / Q000633:toxicity*; D004054:Diethylstilbestrol / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000633:toxicity*; D005347:Fibroblasts; D006801:Humans; D008647:Mesocricetus; D009153:Mutagens; D009630:Nondisjunction, Genetic; D011123:Polyploidy; D013997:Time Factors; D014750:Vincristine / Q000633:toxicity*
D009153:Mutagens; D004958:Estradiol; D014750:Vincristine; D004054:Diethylstilbestrol; D003703:Demecolcine