Selectivity of the antimetastatic and cytotoxic effects of 1-p-(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.
The effects of two 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, have been examined in comparison with those of a cytotoxic agent, cyclophosphamide, in mice bearing Lewis carcinoma. Cyclophosphamide at the two highest dosages causes a strictly related and pronounced inhibition (to less than 10%) of the weight of the s.c. 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 three dosages used, (+/-)-1,2-di(3,5-dioxopiperazin-1-yl)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 s.c. 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 three 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 s.c. tumors. In hosts pretreated with DM-COOK, no reduction in the formation either of spontaneous or of artificial metastases is observed. These data indicate that DM-COOK acts directly on tumor cells and that it presumably inhibits their release from the primary tumor into the bloodstream.
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D003520:Cyclophosphamide / Q000494:pharmacology / Q000633:toxicity; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D009362:Neoplasm Metastasis / Q000517:prevention & control; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009360:Neoplastic Cells, Circulating; D010879:Piperazines / Q000494:pharmacology*; D011929:Razoxane / Q000494:pharmacology* / Q000633:toxicity; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014226:Triazenes / Q000494:pharmacology* / Q000633:toxicity
D000970:Antineoplastic Agents; D010879:Piperazines; D014226:Triazenes; D011929:Razoxane; C030838:1-(4-carboxyphenyl)-3,3-dimethyltriazene; D003520:Cyclophosphamide; D013936:Thymidine