SELECTIVITY OF THE ANTI-METASTATIC AND CYTO-TOXIC EFFECTS OF 1-PARA-(3,3-DIMETHYL-1-TRIAZENO)BENZOIC ACID POTASSIUM-SALT, (+/-)-1,2-DI(3,5-DIOXOPIPERAZIN-1-YL)PROPANE, AND CYCLOPHOSPHAMIDE IN MICE BEARING LEWIS LUNG-CARCINOMA

  • 1 January 1981
    • journal article
    • research article
    • Vol. 41  (6) , 2524-2528
Abstract
The effects of 2 selective antimetastatic agents, 1-p-(3,3-dimethyl-1-triazeno)benzoic acid potassium salt (DM-COOK), and (.+-.)-1,2-di(3,5-dioxopiperazin-1-yl)propane, were examined in comparison with those of a cytotoxic agent, cyclophosphamide, in mice bearing Lewis lung carcinoma. Cyclophosphamide at the 2 highest dosages causes a strictly related and pronounced inhibition (to less than 10%) of the weight of the subcutaneous tumor, spontaneous metastases and lung colonies formed after i.v. injection of tumor cells (artificial metastases); this behavior is consistent with a purely cytotoxic mechanism. At the 3 dosages used, (.+-.)-1,2-di(3,5-dioxopiperazin-1yl)propane reduces the weight of spontaneous metastases to less than 3%. A dose-dependent reduction of artificial metastasis weight is also observed. At the highest dose, artificial metastasis weight is reduced to about 5% and subcutaneous tumor mass is significantly lowered to 40%. These effects are consistent with the combined occurrence of cytotoxic and selective antimetastatic action, although the latter appears to be predominant. At the 3 dosages used, DM-COOK markedly depresses the weight and number of spontaneous metastases to about 10%, leaving the formation of artificial metastases unaffected and causing no significant effect on primary tumor growth. The effects of these agents on the fractional incorporation of [3H]thymidine in tumor cells further indicate that only DM-COOK is devoid of cytotoxic effects for pulmonary and subcutaneous tumors. In hosts pretreated with DM-COOK, no reduction in the formation either of spontaneous or of artificial metastases is observed. DM-COOK acts directly on tumor cells and presumably inhibits their release from the primary tumor into the bloodstream.