Colcemid-induced neoplastic transformation and aneuploidy in Syrian hamster embryo cells

Abstract

Treatment of Syrian hamster embryo cells in culture with 0.01-0.1 micrograms/ml of colcemid for 48 h resulted in morphological and neoplastic transformation of the cells. Cell transformation was observed with doses which were non-cytotoxic and did not cause mitotic inhibition of the cells. Higher dose of colcemid (greater than 0.1 microgram/ml) resulted in mitotic inhibition of the cells and a significant loss of colony forming ability, but no increase in the frequency of morphological transformation. Treatment of the cells with transforming doses of colcemid did not result in any measurable induction of gene mutations or structural chromosome aberrations; however, numerical chromosome changes in the treated cells were observed. A 14-fold increase in the number of aneuploid cells with a near diploid chromosome complement was found in cultures treated with 0.1 micrograms/ml colcemid and both chromosome loss and gain were induced. The dose response curves for colcemid induced morphological transformation and aneuploidy were similar. These results are consistent with a role of carcinogen-induced chromosome non-disjunction in carcinogenesis.

Aneuploidy correlated 100% with chemical transformation of Chinese hamster cells

“…It has been shown that colcemid causes aneuploidy in CHE cells (79) and also transforms Syrian Hamster cells in culture (81). Following these procedures, we have treated CHE cells with 0.02 g͞ml colcemid thrice for 2 days in consecutive transfers.…”

Aurora-B/AIM-1 kinase activity is involved in Ras-mediated cell transformation

“…Furthermore, classical transformation experiments have suggested that a spindle-disrupting drug, colcemid, is carcinogenic due to changes in the chromosome number (Tsutsui et al, 1984). We therefore examined the effect of spindle-disorganizing drugs on BALB/c 3T3 A31-1-1 cells, which are susceptible to physical and chemical carcinogens (Kakunaga and Crow, 1980), as well as various oncogenes (Tatsuka et al, 1996).…”

“…However, both of them induce not only perturbations of chromosome number but also carcinogenicity after a long period of cultivation (Tsutsui et al, 1984;Ota et al, 2002). In classical transformation experiments, the long-term culture of rodent cells is generally known to induce spontaneous transformation, a process caused by activation of certain endogenous retroviral or cellular oncogenes.…”

Bisphenol-A induces cellular transformation, aneuploidy and DNA adduct formation in cultured Syrian hamster embryo cells

“…Pfeiffer et al (1996Pfeiffer et al ( , 1997 reported aneuploidogenic properties of BP-A, i.e., inhibition of microtubule (MT) assembly in intact cells and under cell-free conditions and induction of both metaphase arrest and micronuclei-containing chromatids or whole chromosomes in cultured Chinese hamster V79 cells. Chemical compounds inducing numerical chromosomal changes, such as Colcemid and vincristine sulfate, have been demonstrated to cause morphological and neoplastic transformations of cultured Syrian hamster embryo (SHE) cells (Tsutsui et al, 1984(Tsutsui et al, , 1986. 17␤-Estradiol (E 2 ) and the synthetic estrogen diethylstilbestrol (DES) also induce numerical chromosomal changes (i.e., aneuploidy) and cellular transformation in SHE cells (Tsutsui et al, 1983(Tsutsui et al, , 1987(Tsutsui et al, , 1997.…”