In vivo studies on the mechanism of action of the tumor inhibitor vernolepin in the Walker 256 carcinosarcoma.

Rats bearing the Walker 256 intramuscular carcinosarcoma were treated intraperitoneally with tritium-labeled vernolepin or with its nontumor-inhibitory methanol adduct. Following treatment with 3H-vernolepin on several different dosage schedules, the tumors were found to contain significantly more radioactivity per gram wet weight than control tissue (muscle from the contralateral limb). After the administration of the nontumor-inhibitory methanol adduct, no such difference was observed. The distribution of radioactivity in various other organs (liver, kidney, spleen, intestine, lung, heat, fat, blood, and brain) was measured following treatment with the parent compound (3H-vernolepin). The implications of these data in terms of the suggested mechanism of action of sesquiterpene lactone tumor inhibitors is discussed.