Effect of the antitumour agent 5-(3,3-dimethyl-1-triazeno imidazole-4-carboxamide (DTIC) on cyclic AMP levels in intact MH1C1 hepatoma cells

Addition of the cytostatic agent 5-(3,3-dimethyl-1-triazeno)-imidazole-carboxamide (DTIC, dacarbazin) to MH1C1 hepatoma cells, alone or in combination with adrenaline, was shown to elevate intracellular cyclic AMP. The cyclic AMP level was increased from basal values of about 0.40 to about 0.75 pmol/mg protein 10 min. after DTIC addition. Accumulation of cyclic AMP in response to a supramaximal concentration of adrenaline is amplified in a dose-dependent way by 0.1-2 mM DTIC. The effect is apparently due to inhibition of cyclic AMP breakdown, since DTIC inhibits the low-Km form of the cyclic AMP phosphodiesterase without significantly affecting the adenylate cyclase activity of MH1C1 homogenates.