Genetic instability of cell lines derived from a single human small cell carcinoma of the lung

TY - JOUR

T1 - Genetic instability of cell lines derived from a single human small cell carcinoma of the lung

AU - Engelholm, S A

AU - Vindeløv, L L

AU - Spang-Thomsen, M

AU - Brünner, N

AU - Tommerup, N

AU - Nielsen, M H

AU - Hansen, H H

N1 - Keywords: Carcinoma, Small Cell; Cell Line; Chromosome Aberrations; Clone Cells; DNA, Neoplasm; Flow Cytometry; Humans; Karyotyping; Lung Neoplasms; Male; Microscopy, Electron; Middle Aged

PY - 1985

Y1 - 1985

N2 - Specimens from a human small cell carcinoma of the lung were established as a cell line in vitro. Flow cytometric DNA analysis demonstrated only one tumor cell population in the parent tumor as well as in the early passages in vitro. After six passages in vitro, two new subpopulations with different DNA content appeared. By cloning, permanent cell lines were established from the new subpopulations, whereas the original population stopped growing. The cloned cell lines were characterized by morphology, chromosomes analysis, electron microscopy and plating efficiency; the stability of the DNA content was examined regularly by flow cytometric DNA analysis and instability was found in one of the cloned cell lines. Chromosome analysis showed that the cloned cell lines consisted of more than one population after 17 in vitro passages. Both cloned cell lines produced tumors in nude mice. Genetic instability was demonstrated in these mouse-grown tumors as well. Development of resistance to antineoplastic treatment may be due to heterogeneity in sensitivity among subpopulations in a tumor. Isolation of populations with different DNA contents allows the study of interaction between subpopulations and the observations provide evidence in support of the hypothesis of clonal evolution.

AB - Specimens from a human small cell carcinoma of the lung were established as a cell line in vitro. Flow cytometric DNA analysis demonstrated only one tumor cell population in the parent tumor as well as in the early passages in vitro. After six passages in vitro, two new subpopulations with different DNA content appeared. By cloning, permanent cell lines were established from the new subpopulations, whereas the original population stopped growing. The cloned cell lines were characterized by morphology, chromosomes analysis, electron microscopy and plating efficiency; the stability of the DNA content was examined regularly by flow cytometric DNA analysis and instability was found in one of the cloned cell lines. Chromosome analysis showed that the cloned cell lines consisted of more than one population after 17 in vitro passages. Both cloned cell lines produced tumors in nude mice. Genetic instability was demonstrated in these mouse-grown tumors as well. Development of resistance to antineoplastic treatment may be due to heterogeneity in sensitivity among subpopulations in a tumor. Isolation of populations with different DNA contents allows the study of interaction between subpopulations and the observations provide evidence in support of the hypothesis of clonal evolution.

M3 - Journal article

C2 - 2995041

SN - 0277-5379

VL - 21

SP - 815

EP - 824

JO - European Journal of Cancer and Clinical Oncology

JF - European Journal of Cancer and Clinical Oncology

IS - 7

ER -