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J P Roscoe

Publications and source records attributed to J P Roscoe.

At least 19 recordsLinked to original sources
PubMed1989

A comparison of the effect of several factors on the plasminogen activator activity of cloned lines from an ethylnitrosourea-induced glioma and from normal tissue.

Cells from gliomas induced by N-ethyl-N-nitrosourea have a high basal level of plasminogen activator activity compared with cells from normal tissue. Plasminogen activator activity is known to be affected by many substances but whether inhibition or stimulation occurs depends on the cell and agent involved. It is not clear whether tumour and control cells from the same type of tissue respond similarly. A comparison has been made of the effect of several factors on both cell associated and secreted enzyme activity of cloned lines from a glioma and normal tissue. The effect of two cAMP elevating compounds was stimulatory while that of the steroid, dexamethasone, was generally inhibitory for both cells. However, the polypeptide hormone, epidermal growth factor, had a differential effect. It caused an increase in secreted enzyme activity in the tumour line but had no such effect on the control clone. The precise mechanism by which this occurs is unknown. Co-operative effects of the enzyme and growth hormone could result in more aggressive behaviour of the tumour cells.

Animals↗
PubMed1986

An increase in plasminogen activator mRNA occurs at an early stage in ethylnitrosourea-induced transformation of rat brain cells.

Brain tumor cells cultured after transplacental induction by the nitrosamide, N-ethyl-N-nitrosourea had a higher level of plasminogen activator activity than control cells from adult rat brain. Cultures (BE10) derived 2 days after exposure to the carcinogen showed a rise in this proteolytic activity at the 17th passage but were not able to form colonies in agar or tumours in syngeneic rats until passages 44/45. Cultures (BE11) derived 2 days after exposure to buffer did not show a rise in this enzyme activity nor were they able to grow in agar or animals at comparable passages. Zymography and inhibition studies showed that the enzyme produced by the tumour cells was related to human tissue-type plasminogen activator rather than to urokinase. Northern blot analysis showed a higher level of tissue plasminogen activator related mRNA in tumour cells than control cells. There was an increase in mRNA level during passaging of the carcinogen-exposed culture, BE10, which correlated with the increased enzyme activity. There was no rise in the barely detectable mRNA levels of the comparable buffer-exposed culture, BE11. The results suggest that alteration in the transcriptional control of this proteolytic enzyme occurs at an early stage in the transformation process.

Animals↗
PubMed1980

The fine structure of cloned cells from normal adult rat brain.

A cell clone was isolated from a normal rat brain culture and maintained in vitro for many passages. It possessed glial characteristics; in particular ultrastructural examination revealed astrocytic features including the presence of filaments 9--11 nm in diameter.

Animals↗
PubMed1980

Differences in pattern and level of plasminogen activator production between a cloned cell line from an ethylnitrosourea-induced glioma and one from normal adult rat brain.

The production of plasminogen activator (PA) by two cloned cell lines, one from an ethylnitrosourea-induced glioma (A15A5) and the other from normal adult rat brain (ARBO C9), has been investigated. Three assays were used to detect and measure PA in harvest fluids, cells and cell lysates. Similar levels were detected in harvest fluids from both cell lines. However, the cell and lysate assays indicated much higher levels in the tumor line. When actively growing cells were compared A15A5 cells had approximately 16X more fibrinolytic activity than the control cells with a limit of detection in the order of 10(3) cells or 1 microgram protein (cell lysate). In contrast for the control cells PA could only be detected when upwards of 10(4) cells or 5-10 micrograms protein were assayed. Plaminogen activator in as few as 10(3) tumor cells could be detected in the presence of 10(4) non-tumor cells. Plasminogen activator in 26 micrograms protein of A15A5 cell lysate could also be detected in the presence of 44 micrograms protein from ARBO C9 lysates indicating no inhibitory activity in the control cell lysates. Levels of PA in both harvest fluids and cell lysates were determined as cultures progressed through the growth cycle. For cell lysates this showed a build-up of PA in the normal cell line as the cells approached and attained confluence. A much higher level was measured in the tumor cells soon after seeding and maintained to confluence. No differences in growth cycle-associated changes in secreted PA could be determined in harvest fluids: both cell lines showing similar levels at confluence.

Animals↗
PubMed1980

Effect of 12-O-tetradecanoylphorbol-13-acetate on two charateristics of transformation acquired sequentially by ENU-exposed rat brain cells.

Cultures derived from rat brains at different times during the latent period of brain-tumour induction by N-ethyl-N-nitrosourea (ENU) showed increased plasminogen activator (PA) activity before being able to form colonies in agar. Control cultures from buffer-exposed animals showed neither property at comparable passages. More detailed investigations, using a culture derived from foetal brains only 2 days after exposure to ENU and clones from this culture, showed a sequence of low PA activity, then increased activity, followed by the ability to form colonies in agar, suggesting progressive transformation of cells in culture. Continuous culturing in the presence of the mouse skin tumour promoter, 12-O-tetradecanoylphorbol-13-acetate (TPA), did not accelerate the rate at which these two properties were acquired, but did cause a much greater increase of PA activity once this started to rise. If included in the assay mixture TPA also increased the PA activity of the cells. It therefore appears that in this system TPA can modulate PA activity under certain circumstances.

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PubMed1979

Survival of cells implanted in the embryonic chick limb bud: a difference between normal and malignant rat brain cells.

Cells from normal rat brain tissue did not survive and few cells could be found 1 d after grafting. In contrast, cells from a glioma and a carcinogen-treated rat brain survived well and many mitoses were observed. These malignant cells also invaded the limb. The behaviour of normal and malignant cells was followed at shorter times after grafting and some invasion by the normal cells was detected. The first signs of degeneration of normal cells were apparent around 7 h after grafting, and after this the grafts progressively deteriorated. These results support the ideal that the ability of cells to survive and grow in embryonic tissues is a characteristic of malignant cells. The findings are discussed in relation to mechanisms of tumour formation.

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PubMed1979

Cellular heterogeneity in an ethylnitrosourea-induced glioma: malignancy, karyology and other properties of tumour cell types.

Two types of tumour cell have been obtained from a glioma transplacentally induced by ethylnitrosourea in a BD-IX rat. These were distinguished in culture by their different morphologies, responses to dibutyryl cyclic adenosine monophosphate, inducibility of glycerol phosphate dehydrogenase and growth in soft agar. They had different karyotypes, with distinctive numbers and arrangements of chromosomes. One cell type had an apparently normal diploid set of 42 whilst the other had 43 chromosomes. An additional chromosome No 4 was identified in the latter by Giemsa banding. Translocations and other abnormalities involving this chromosome were consistently observed. Both cell types produced malignant, astrocytic tumours when injected into newborn syngeneic rats, but with different latent periods and morphological features.

Animals↗
PubMed1978

Fibrinolytic activity of cultured cells derived during ethylnitrosourea-induced carcinogenesis of rat brain.

Using a fibrin-agarose-overlay technique, high levels of plasminogen-dependent fibrinolytic activity have been demonstrated in cell lines derived from an ethylnitrosourea-induced glioma of the rat brain. Cell lines derived from normal adult rat brain showed only low levels of activity. The degree of lysis produced by a cell line was dependent on the average number of cells per colony, and a different pattern of response was observed for tumour and normal cell lines. A good positive correlation existed between the level of fibrinolytic activity, growth in agar and tumourigenicity of a cell line. Fibrinolytic activity was associated with cell lines derived at various times in the latent period, before the appearance of a visible tumour. Many cell lines derived from rat brains at 57-60 (E7), 90-91 (E8) and 111-112 (E6) days after transplacental exposure to ethylnitrosourea showed fibrinolytic activity, and in the latter group the close association with growth in agar and tumourigenicity was also demonstrated. Results from cell lines derived in the E7 and E8 experiments indicated that the possession of fibrinolytic activity preceded the ability of cells to form colonies in agar.

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PubMed1976

Studies of the morphology and tumorigenicity of experimental brain tumours in tissue culture.

Brain tumours induced transplacentally in BD-IX rats by a single dose of N-ethyl-N-nitrosourea have been successfully grown in tissue culture. These tumours were malignant pleomorphic gliomas. The cultured cells retained their glial morphology both in vitro and on reinjection into syngeneic hosts: astrocytes became the predominant cell type. The ability of the cells to form tumours increased with time in culture as reflected both in the decreased latency of the tumours and in the increased ability of the cells to grow in semi-solid medium.

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