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• W1989052002 abstract "Abstract The effect of anti-tumour alkylating agents on the adenosine 3′,5′-monophosphate (cyclic AMP) levels of sensitive and resistant Walker carcinoma cells in tissue culture has been investigated. Chlorambucil caused a two-fold elevation of cyclic AMP, in the sensitive line only, 8 hr after treatment with a dose of 5 μg/ml. A comparable increase is produced by the cyclic nucleotide phosphodiesterase inhibitor aminophylline at a dose which produces the same degree of inhibition of cell growth. The therapeutically-inactive monofunctional N -ethyl analogue of chlorambucil had no effect on the cyclic AMP level of the sensitive cells at a dose of 250 μg/ml after 8 hr, while the highly selective monofunctional alkylating agent, CB 1954, at 1 μg/ml caused an elevation of cyclic AMP in the sensitive line 24 hr after treatment. This is not a non-specific effect caused by an inhibition of cell growth for the antimetabolite methotrexate had no effect on the intracellular cyclic AMP of sensitive Walker cells at doses which produced complete inhibition of cell growth. The effect of the alkylating agents on cyclic AMP levels is probably due to a specific inhibition of the cyclic nucleotide phosphodiesterase with a low K m value, since only this form of the enzyme is inhibited, and only in the sensitive cells, when an effect on cell growth and cyclic AMP content is observed. In the case of CB 1954, however, there was no inhibition of either form of the phosphodiesterase at a time when cyclic AMP levels were elevated. A linear relationship exists between the reciprocals of the intracellular cyclic AMP and the percentage growth inhibition produced by a given dose of chlorambucil." @default.
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• W1989052002 date "1975-01-01" @default.
• W1989052002 modified "2023-09-25" @default.
• W1989052002 title "Inhibition of cyclic 3′,5′-nucleotide phosphodiesterase—a possible mechanism of action of bifunctional alkylating agents" @default.
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• W1989052002 doi "https://doi.org/10.1016/0006-2952(75)90279-8" @default.
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