Effect of the Antitumour Agent 5‐(3,3‐Dimethyl‐1‐triazeno imidazole‐4‐carboxamide (DTIC) on Cyclic AMP Levels in Intact MH₁C₁ Hepatoma Cells

Abstract

Absrrari: Addition of the cytostatic agent 5-(3,3-dimethyl-I-triazeno)-imidazole-carboxamide (DTIC, dacarbazin) to MHlCl 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 0.40to 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-K, form of the cyclic AMP phosphodiesterase without significantly affecting the adenylate cyclase activity of MHlCl homogenates. K q p~~o r d s tHepatoina cellscyclic AMP -DTICdacarbazincell culture.