Chemotherapeutic effects of 13 nitrosoureas on the LSA lymphoma ascites tumor of the C57BL mouse.
The LSA lymphoma of the C57BL/ym mouse has been used to test 13 nitrosoureas for cure of advanced tumors and for induced tumor resistance (ITR) of surviving animals. Tumors were initiated by intraperitoneal inoculation of 10(6) LSA cells. Controls died in 8-9 days. Five-day old tumors were defined as advanced tumors, and treatment consisted of a single dose of a nitrosourea to groups of 10 male mice, 8-9 weeks old, for each compound. The nitrosoureas used were: BCNU (NSC-40992), CCNU (NSC-79037), MeCCNU (NSC-95441), chlorozotocin (CLZ) (NSC-178248), streptozotocin (STZN) (NSC-85998) CNU (NSC-47547), FCNU (NSC-87974), GANU (NSC-254174), ACNU (NSC-245382), PCNU (NSC-95466), cis-acid (NSC-153174), 153174), NSC-88104, and GCNU (NSC-114460). The major endpoint assessed was tumor cure and was grouped as follows: (1) high (greater than or equal to 80%), achieved with BCNU, MeCCNU, CCNU, CLZ, ACNU, FCNU, PCNU, and cis-acid; (2) medium (40- less than 80%), obtained with GANU, NSC-88104, and GCNU, and (3) low or nil (less than 40%), shown by CNU and STZN. The second endpoint was treatment-induced ITR. Cured mice, i.e., those surviving over 30 days after death of controls were challenged with 10(5) LSA live cells, and survivors from this challenge were challenged with 10(7) LSA cells 1 month later. Survivors from both inocula were considered highly immune (HI). High percentages of HI mice (greater than or equal to 80%) were obtained from mice cured with MeCCNU, CCNU, ACNU, FCNU, PCNU, and NSC-88104. STZN produced 0.0% cures; the other nitrosoureas showed 33.3-75% HI mice. Cure rates and ITR appeared to be agent- and structure-related. Cure alone did not lead to the resistant state.
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use* / Q000633:toxicity; D004351:Drug Resistance; D007928:Lethal Dose 50; D008223:Lymphoma / Q000188:drug therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D009607:Nitrosourea Compounds / Q000627:therapeutic use* / Q000633:toxicity; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D009607:Nitrosourea Compounds