Infiltration of Liver and Brain by Tumor Cells in Leukemic Mice: Prevention by Dimethyltriazenes and Cyclophosphamide

Abstract

The dimethyltriazenes p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK) and 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) increase, unlike cyclophosphamide (Cy), the survival time of mice bearing L1210 lymphoid leukemia, P388 lymphocytic leukemia and TLX5 lymphoma with a mechanism unrelated to cytotoxicity for tumor cells. The in vivo bioassays of brains, and the histologic examinations of the livers of leukemic mice show that DM-COOK and DTIC prevent leukemic infiltration in these organs at dosages devoid of cytotoxic effects for peritoneal tumor cells. At a dosage equitoxic with that of dimethyltriazenes, cyclophosphamide causes the absence of tumor cells in the peritoneal cavity and in the brains and livers of mice bearing P388 and L1210 leukemias. DM-COOK and DTIC thus possess a mild or insignificant cytotoxic action together with antimetastatic properties also on mouse transplantable leukemias. The use of DM-COOK appears advantageous over that of cyclophosphamide and DTIC because of a reduced host toxicity, which is particularly evident for cyclophosphamide and DTIC on liver parenchyma and bone marrow.

Effects of antimetastatic, antiinvasive and cytotoxic agents on the growth and spread of transplantable leukemias in mice

“…DM-COOK and ICRF-159 have already been shown to possess selective antimetastatic properties, since they prevent the metastatic spread of solid tumors in mice by inhibiting the tumor cell from entering the blood stream [3]. DM-COOK has also been reported to prevent tumor infiltration in the liver and brain of leukemic mice [13], and the data reported here are in agreement with an( support these findings. ICRF-159 does not prevent, at least in the experimental conditions presently employed, leukemic infiltration of the brain in mice bearing L1210 leukemia.…”