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SummaryThe carcinogenic activity of N-isopropyl-α-(2-methylhydrazino)-p-foluamide · HCI (procarbazine hydrochloride) was directly compared in (BALB/c × DBA/2)F<sub>1</sub> mice with that of its degradation products, several hydrazines, and isonicotinic acid hydrazide. Procarbazine hydrochloride and two of its degradation products, N-isopropyl-α-(methylhydrazone)-p-toluamide and N-isopropyl-α-(2-methylazo)-p-toluamide, induced a high incidence of multiple pulmonary tumors. One of the terminal in vivo degradation products of procarbazine, N-isopropyl terepthalamic acid, as well as hydrazine sulfate and isonicotinic acid hydrazide induced a considerably lower incidence of pulmonary tumors than procarbazine with a lower mean nodule count. No carcinogenic activity was observed with other degradation products of procarbazine (N-isopropyl-p-formylbenzamide and methylhydrazine) or with phenylhydrazine, benzylhydrazine, symmetrical dimethylhydrazine, and unsymmetrical dimethylhydrazine, as judged by the low count of lung tumor nodules and the long latent period. In addition to pulmonary tumors, procarbazine and N-isopropyl-α-(2-methylazo)-p-toluamide induced leukemia and cystadenoma of the kidneys. However, there was some indication that sodium carboxymethyl cellulose, used as the vehicle, contributed to the formation of cystadenoma. No leukemia was obtained with any of the other compounds. The data suggest that, while the oxidative degradation products of procarbazine, particularly the azo and hydrazone derivatives, contribute in large part to the induction of multiple pulmonary tumors in mice administered procarbazine, only procarbazine or the azo compound is responsible for the induction of leukemia. |
