Antitumor effect and metabolic activation of cyclophosphamide and 4-hydroperoxycyclophosphamide in the human breast carcinoma (MX-1)-nude mouse system.
The effects of cyclophosphamide (CPA) and its active form, 4-hydroperoxy-CPA, against human breast carcinoma transplanted into nude mice (BALB/c nu/nu) were evaluated in terms of the decreases of hepatic drug-metabolizing enzymes in nude mice. A human breast carcinoma, MX-1, was implanted into the subcutaneous tissue of nude mice and a drug was administered intravenously once at a dose of 0.05, 0.1 or 0.15 mmol/kg, 1 or 3 weeks after tumor inoculation. 4-Hydroperoxy-CPA was more effective than CPA as regards inhibition of tumor growth, and the difference in effect was greater when the drugs were administered 3 weeks after tumor inoculation. The activity of CPA was depressed by the decrease of the hepatic drug-metabolizing enzymes in proportion to the tumor-bearing period. Therefore, the effects of masked derivatives of CPA may correlate with the changes in drug-metabolizing activities of tumor-bearing mice. The human tumor xenografts-nude mice system is considered to be suitable for chemosensitivity tests with masked compounds.
D000328:Adult; D000818:Animals; D001711:Biotransformation; D003520:Cyclophosphamide / Q000031:analogs & derivatives* / Q000378:metabolism / Q000627:therapeutic use*; D003577:Cytochrome P-450 Enzyme System / Q000032:analysis; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
D003520:Cyclophosphamide; D003577:Cytochrome P-450 Enzyme System; C011272:perfosfamide