Antitumor effect of cyclophosphamide on LS and P388 tumors is realized via apoptosis and on HA-1 and Krebs-2 tumors resistant to apoptosis via necrosis of tumor cells. Phenobarbital induction of cyclophosphamide-metabolizing enzymes decreases and cimetidine inhibition potentiates the effect of cyclophosphamide on LS and P388 cells and does not modulate the effect on HA-1 and Krebs-2 cells. Presumably, apoptosis and necrosis of tumor cell are induced by different cyclophosphamide metabolites.
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