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Cure rates and tumor resistance in cured mice after nitrosourea treatment of EMT6 ascites tumors.

Single-dose BCNU or chlorozotocin (CLZ) treatment of EMT6 mammary carcinoma tumors of the BALB/c mouse has only a transient effect on tumor growth, after which tumors follow control growth patterns. To test the hypothesis that drug access to tumor cells might be a factor in cell killing, we adapted the EMT6/KY tumor to ascites form. Injection of 10(5) EMT6/KY cells i.p. kills BALB/c mice with a mean survival time of 13.0 +/- 1.0 days. We have surveyed several nitrosoureas for their effects on the EMT6/KY ascites tumor after intraperitoneal injection of the drugs. Cure rates and percent increase in life span were used as endpoints. Also, we tested for induced host tumor resistance (TR) in cured mice, by challenging survivors with live EMT6 cells. Highest cure rates were obtained for treatment on days 2, 3, or 4 after inocula of 10(5) cells: CLZ (10 mg/kg), 83.3%; cis-acid (20 mg/kg), 75%, and CCNU (30 mg/kg), 70%. Other nitrosoureas, i.e. BCNU, PCNU, GANU, STZN, FCNU, ACNU, MeCCNU, NSC-88104 produced lower cure rates. Cured mice surviving challenges of 10(6) EMT6 cells were considered TR. TR mice did not correlate with cure rates for the 3 nitrosoureas giving high cure rates. As percent of survivors, TR mice were (for day 3 treatment): FCNU, 100%, BCNU, 100.0% and CLZ, 50.0%. Thus, cure rates and TR seem to depend on the structure of the nitrosourea, but through different mechanisms.