A proliferation gradient in three‐dimensional colonies of cultured human glioma cells

The growth of colonies of human glioma cells cultured in agarose has been studied. The mitotic activity and the fraction of cells which incorporated tritiated thymidine decreased nearly exponentially with the depth in the colonies, the shape and inclination of the proliferation gradient being independent of the colony diameter. This explains why the volume doubling times were rather similar for colonies of different sizes. It is also shown that the stability of the gradient during growth gave rise to nearly exponential growth, although a large part of the centrally situated cells were out of the cell cycle or had a reduced proliferative rate. The incorporation of tritiated thymidine into labelled cells was similar in the peripheral and the central regions as evaluated from grain counting. This indicated that the length of the S‐phase was constant.

[1]  P. Rubin,et al.  Microcirculation of tumors Part I: Anatomy, function, and necrosis , 1966 .

[2]  S. Arnott,et al.  The agarose double helix and its function in agarose gel structure. , 1974, Journal of molecular biology.

[3]  B. Westermark,et al.  The deficient density‐dependent growth control of human malignant glioma cells and virus‐transformed glia‐like cells in culture , 1973, International journal of cancer.

[4]  R. Huebner,et al.  Colonial growth in agar of cells derived from adenovirus-induced hamster tumors. , 1967, Journal of the National Cancer Institute.

[5]  A. Polson,et al.  Determination of diffusion coefficients by spreading from thin layers , 1969 .

[6]  R. Sutherland,et al.  Growth of multicell spheroids in tissue culture as a model of nodular carcinomas. , 1971, Journal of the National Cancer Institute.

[7]  P. Dombernowsky,et al.  CYTOKINETIC ANALYSIS OF THE JB‐1 ASCITES TUMOUR AT DIFFERENT STAGES OF GROWTH , 1973, Cell and tissue kinetics.

[8]  V. Terskikh,et al.  ON THE RESTING PERIODS IN THE CELL LIFE CYCLE * , 1969 .

[9]  I. Macpherson.  Soft Agar Techniques , 1973 .

[10]  J. Denekamp,et al.  IN VITRO AND IN VIVO LABELLING OF ANIMAL TUMOURS WITH TRITIATED THYMIDINE , 1973, Cell and tissue kinetics.

[11]  I. Tannock,et al.  ON THE EXISTENCE OF A Go‐PHASE IN THE CELL CYCLE , 1970 .

[12]  L. Schiffer,et al.  CYTOKINETICS OF THE S‐180 ASCITES TUMOR SYSTEM , 1973, Cell and tissue kinetics.

[13]  J. Smith,et al.  Do cells cycle? , 1973, Proceedings of the National Academy of Sciences of the United States of America.

[14]  M. Rajewsky,et al.  In vitro studies of cell proliferation in tumours. II. Characteristics of a standardised in vitro system for the measurement of 3H-thymidine incorporation into tissue explants. , 1965, European journal of cancer.