Toxicity to tumour cells of diethylaminoreserpine.

Diethylaminoreserpine (DL-152), an inhibitor of cyclic AMP phosphodiesterase, has been shown to kill clonogenic cells of the KHT fibrosarcoma when the drug is given intraperitoneally to the tumour-bearing mouse. DL-152 shows a greater toxicity to acutely hypoxic cells than to aerated cells. Following DL-152 injection, the number of surviving clonogenic tumour cells fell progressively until a minimum level was reached at 48 h after injection; repopulation commenced immediately and proceeded rapidly. The extent of cell killing following DL-152 injection was directly proportional to the size of the tumour at the time of treatment. A single injection of DL-152 produced no measurable change in the growth rate of small tumours. Treatment of larger tumours however, induced a period of slow growth followed by a return to the rate of growth observed in controls.