Inhibition of large intestinal cancers by celecoxib using a serial sacrifice technique.
In this serial sacrifice experiment, celecoxib (C) was administered at a 0.1% dose level, in the diet of female Swiss Webster CFW outbred mice. The animals also received either 1,2-dimethylhydrazine dihydrochloride (1,2-DMH) as ten weekly subcutaneous (s.c.) injections at 20 microg/g body weight or physiological saline (PS) as ten weekly s.c. injections at 0.01 ml/g body weight. Subsequently, the mice were sacrificed at 26 weeks or 35 weeks after the first injection of 1,2-DMH or PS. The number of mice with large intestinal tumors and the total number of these tumors were: Group 1 (1,2-DMH), 29 and 438; Group 2 (C + 1,2-DMH), 18 and 64; and Group 3 (PS), 1 and 1, in the mice sacrificed at 26 weeks. The corresponding tumor incidences in the mice sacrificed at 35 weeks were: Group 1 (1,2-DMH), 30 and 323; Group 2 (C + 1,2-DMH), 23 and 134; and Group 3 (PS), 0 and 0. Histopathologically, the tumors were diagnosed as polypoid adenomas and adenocarcinomas of the cecum, colon and rectum. Celecoxib treatment inhibited the development of large intestinal cancers in mice sacrificed at 26 or 35 weeks after the first injection of the carcinogen.
Toth
Bela
B
The Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha 68198, USA. btoth@unmc.edu
Coles
Melissa
M
D019813:1,2-Dimethylhydrazine / Q000008:administration & dosage / Q000494:pharmacology; D000230:Adenocarcinoma / Q000139:chemically induced / Q000473:pathology; D000236:Adenoma / Q000139:chemically induced / Q000473:pathology; D000284:Administration, Oral; D000818:Animals; D021461:Animals, Outbred Strains; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D002273:Carcinogens / Q000008:administration & dosage / Q000494:pharmacology; D000068579:Celecoxib; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D015994:Incidence; D007279:Injections, Subcutaneous; D007414:Intestinal Neoplasms / Q000139:chemically induced / Q000453:epidemiology / Q000401:mortality / Q000473:pathology / Q000517:prevention & control*; D051379:Mice; D009374:Neoplasms, Experimental / Q000139:chemically induced / Q000453:epidemiology / Q000401:mortality / Q000517:prevention & control*; D011720:Pyrazoles / Q000008:administration & dosage / Q000494:pharmacology*; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*; D015996:Survival Rate; D013997:Time Factors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002273:Carcinogens; D016861:Cyclooxygenase Inhibitors; D011720:Pyrazoles; D013449:Sulfonamides; D019813:1,2-Dimethylhydrazine; D000068579:Celecoxib