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Rapid changes in nucleoside transport induced by growth inhibitors. Studies with neoplastic mast cells
Abstract:
Aqueous extracts of murine embryonic or uterine tissue, or [(6)N]O(2)'-dibutyryl 3',5'-adenosine monophosphate (dbc-AMP) which were cytostatic for the murine mastocytoma P815Y in vitro also induced rapid changes in the incorporation of exogenous nucleosides into acid-insoluble material. However, these alterations were not a consequence of growth arrest. Different dose-response curves were obtained for cytostasis and inhibition of [(3)H]-nucleoside incorporation, and changes in [(3)H]thymidine uptake were detected within 15 min of treatment with the inhibitors. Also, there were differential effects of each inhibitor on the incorporation of (3)H-labeled thymidine, uridine, adenosine, or choline into acid-insoluble material.
Insights
Murine mastocytoma P815Y cells treated with tissue extracts or dibutyryl cyclic AMP (dbc-AMP) showed rapid changes in nucleoside incorporation, independent of growth arrest. These inhibitors affected different nucleoside uptakes distinctly.
Area of Science:
- Biochemistry
- Cell Biology
- Pharmacology
Background:
- Murine mastocytoma P815Y cells are a model for studying cytostatic agents.
- Cytostatic agents can impact cellular metabolism and macromolecular synthesis.
Purpose of the Study:
- To investigate the effects of aqueous tissue extracts and dibutyryl cyclic AMP (dbc-AMP) on nucleoside incorporation in P815Y cells.
- To determine if observed changes in nucleoside incorporation are linked to cytostasis or growth arrest.
Main Methods:
- Treatment of P815Y cells with aqueous murine embryonic/uterine tissue extracts or dbc-AMP.
- Measurement of exogenous nucleoside incorporation into acid-insoluble material.
- Analysis of dose-response curves for cytostasis and nucleoside incorporation inhibition.
- Assessment of short-term (15 min) effects on [(3)H]thymidine uptake.
Main Results:
- Both tissue extracts and dbc-AMP induced rapid alterations in exogenous nucleoside incorporation.
- These alterations were not a direct consequence of growth arrest.
- Distinct dose-response curves were observed for cytostatic effects versus inhibition of nucleoside incorporation.
- Differential effects on the incorporation of thymidine, uridine, adenosine, and choline were noted.
Conclusions:
- Aqueous tissue extracts and dbc-AMP modulate nucleoside incorporation in P815Y cells through mechanisms separate from growth arrest.
- The observed effects suggest complex regulatory pathways influencing nucleotide metabolism in response to these agents.