Chemoprevention by indomethacin of N-butyl-N-(4-hydroxybutyl)-nitrosamine-induced urinary bladder tumors.
The effects of indomethacin on the development of N-butyl-N-(4-hydroxybutyl) nitrosamine (OH-BBn)-induced urinary bladder tumors were evaluated in male BDF mice. Preliminary feeding studies revealed that the highest non-toxic dose of indomethacin was 15 mg/kg of AIN-76A diet; thus, dose levels of 15 and 7.5 mg/kg of diet were selected to determine the chemopreventive efficacy of this agent. Diet supplementation with indomethacin was initiated when the mice were 49 days old and continued for the duration of the study. Starting one week after indomethacin treatment, OH-BBN was administered 1x/week for eight weeks. Upon termination of the study (180 days after the initial carcinogen administration), all tumors in the urinary bladder were removed and classified histologically. Mice receiving carcinogen and no indomethacin supplementation had a 24% incidence of urinary bladder tumors; mice receiving 7.5 mg/kg and 15 mg of indomethacin had a 5% and 0% incidence of urinary bladder tumors, respectively. The significant reduction of OH-BBN-induced urinary bladder tumors by indomethacin is consistent with previous suggestions that prostaglandin synthesis inhibitors are effective inhibitors of carcinogenesis.
Grubbs
C J
CJ
Department of Nutrition Sciences, University of Alabama, Birmingham 35294.
Juliana
M M
MM
Eto
I
I
Casebolt
T
T
Whitaker
L M
LM
Canfield
G J
GJ
Manczak
M
M
Steele
V E
VE
Kelloff
G J
GJ
D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002085:Butylhydroxybutylnitrosamine; D002278:Carcinoma in Situ / Q000139:chemically induced / Q000517:prevention & control; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000517:prevention & control; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced / Q000517:prevention & control; D004305:Dose-Response Relationship, Drug; D007213:Indomethacin / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D010212:Papilloma / Q000139:chemically induced / Q000517:prevention & control; D013997:Time Factors; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000517:prevention & control*
D016588:Anticarcinogenic Agents; D002085:Butylhydroxybutylnitrosamine; D007213:Indomethacin