Non‐random distribution of abnormal mitoses in heteroploid cell lines

Dooley, William C.; Allison, David C.

doi:10.1002/cyto.990130503

Cited by 8 publications

(6 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In several earlier publications supporting this concept it was suggested that heteroploid cells with non-modal DNA contents were destroyed at mitosis and did not reach telophase (Hsu & Moorhead 1956, Stich 1959, Stich & Steel 1962a. In contrast to these results, recent studies in our laboratory have shown the presence of significant proportions of telophase cells with non-modal DNA contents in several heteroploid cell populations (Dooley & Allison 1991, Dooley & Allison 1992.…”

Section: Discussioncontrasting

confidence: 82%

Evidence for altered cell‐cycle traverse of the non‐modal cells of the heteroploid MCa‐11 line

et al. 1993

View full text Add to dashboard Cite

Classic stem cell theory states that the growth of heteroploid cell populations is due to the proliferation of 'main stemline' cells with modal DNA content and chromosome number. Cells with non-modal DNA content and chromosome number are thought to be blocked and/or destroyed at mitosis. To test this, we studied two chromosomally stable cell populations (mouse bone marrow and WCHE-5 cells) and one heteroploid, chromosomally diverse cell line (MCa-11). The heteroploid MCa-11 cells showed significant [3H]dT labelling for cells with DNA contents below the modal G0/G1 peak and above the modal G2 peaks (P < 0.001). This was consistent with the presence of cells with the non-modal DNA content that were engaged in replicative DNA synthesis. A percentage labelled mitosis analysis showed that MCa-11 cells with non-modal DNA content and chromosome number were able to complete mitosis, although with prolonged pre-karyokinetic time. These results suggest that many non-modal cells present in heteroploid cell populations are capable of continued proliferation.

show abstract

Section: Discussioncontrasting

confidence: 82%

Evidence for altered cell‐cycle traverse of the non‐modal cells of the heteroploid MCa‐11 line

et al. 1993

View full text Add to dashboard Cite

show abstract

“…Endoreduplicated cells were seen at low frequency (1-3%), but only in the inducible Ha-ras cells after exposure to IPITG. It has been noted that tumor cells with divergent karyotypes eventually achieve a modal but aneuploid chromosome or DNA content (36), suggesting that there may be a selective pressure for cells to revert to genetic stability. In contrast to G5 cells, 242 cells had been in extended culture for sufficient time to select for mutations that suppress genomic instability but not the transformed phenotype.…”

Section: Resultsmentioning

confidence: 99%

The human Ha-ras oncogene induces genomic instability in murine fibroblasts within one cell cycle.

Denko

Giaccia

Stringer

et al. 1994

Proc. Natl. Acad. Sci. U.S.A.

195

121

View full text Add to dashboard Cite

show abstract

“…The authors proposed that this process allows the nonmodal cells to contribute continuously to the genetic diversity of the modal peak. 38 A subsequent study demonstrated that nonmodal cells were capable of continued cell proliferation but were delayed temporarily in the G 2 and/or the prophase-metaphase stages of the cell cycle relative to cells with a modal DNA content. 39 Our data support this hypothesis in that the informational content of the diploid or pseudo-diploid cells of the tumorigenic populations obviously differs from that of the diploid cells of the nontumorigenic founding population of WB-F344 cells.…”

Section: Discussionmentioning

confidence: 99%

Genomic fluidity is a necessary event preceding the acquisition of tumorigenicity during spontaneous neoplastic transformation of WB-F344 rat liver epithelial cells

et al. 1998

View full text Add to dashboard Cite

The genomic evolution of a cohort of WB-F344 rat liver epithelial cell lineages undergoing spontaneous neoplastic transformation was followed to define the mechanistic relationship between genomic instability and progression to the neoplastic phenotype. Eighteen independent populations of WB-F344 cells (initiated from a single diploidfounding population) were subjected to 12 cycles of selective growth at confluent cell density, and cellular DNA contents were measured after each selection cycle. Flow cytometry demonstrated significant gains in the amount of G 1 DNA after selection cycles 3, 6, and 7 in 44% (8 of 18), 89% (16 of 18), and 39% (7 of 18) of the cell populations, respectively. All populations subsequently lost DNA and returned to a diploid or pseudo-diploid DNA content within 1 to 2 selection cycles after the appearance of an increased DNA content. Additionally, appearance and subsequent disappearance of aneuploid or tetraploid subpopulations was observed in 11% (2 of 18) and 83% (15 of 18) of the experimental lineages, respectively. Although perturbations of G 1 DNA content were apparent as early as selection cycle 3, at least 8 cycles of selective growth were required for the acquisition of tumorigenicity. While the independent lineages demonstrated significant fluctuations in G 1 DNA content between selection cycles 3 and 8, the majority (11 of 13) of the populations contained a diploid or pseudodiploid DNA content at the time tumorigenicity was expressed. Genomic instability preceded the acquisition of tumorigenic potential in rat liver epithelial cells subjected to selective growth conditions of maintenance at confluence, and may be required for its expression. (HEPATOLOGY 1998;28:78-85.) DNA content analysis by flow cytometry is a useful prognostic indicator of neoplasia. In many solid tumors, a diploid DNA pattern is associated with better patient survival than an aneuploid DNA pattern, which often predicts poor patient survival. Flow cytometric analyses of the relationship between DNA ploidy pattern and patient prognosis in human hepatocellular carcinoma have produced conflicting results. A positive correlation has been reported between a diploid DNA pattern, small tumor size (Ͻ5 cm), and low tumor grade. [1][2][3][4][5] However, the significance of this correlation as it relates to patient prognosis is not clear. Tumor diploidy has been demonstrated to be positively correlated with long-term patient survival in some, [2][3][4]6,7 but not other studies. 1,5,[8][9][10] In fact, Ng et al. 11 found that a diploid DNA pattern was associated with poorer patient survival than was an aneuploid pattern in large hepatocellular carcinomas. A diploid DNA content in a tumor does not preclude the possibility that small chromosomal alterations such as balanced translocations, point mutations, and deletions are present in the tumorigenic cells. Such subtle lesions may not be detected by flow cytometry. Alternatively, the finding of diploidy in a tumor may not preclude that the tumorigenic cells underwent a ...

show abstract

Non‐random distribution of abnormal mitoses in heteroploid cell lines

Cited by 8 publications

References 17 publications

Evidence for altered cell‐cycle traverse of the non‐modal cells of the heteroploid MCa‐11 line

Evidence for altered cell‐cycle traverse of the non‐modal cells of the heteroploid MCa‐11 line

The human Ha-ras oncogene induces genomic instability in murine fibroblasts within one cell cycle.

Genomic fluidity is a necessary event preceding the acquisition of tumorigenicity during spontaneous neoplastic transformation of WB-F344 rat liver epithelial cells

Contact Info

Product

Resources

About