Chemoprevention of the naturally occurring carcinogen 1-hydroxyanthraquinone-induced carcinogenesis by the nonsteroidal anti-inflammatory drug indomethacin in rats.
The chemopreventive effect of the nonsteroidal anti-inflammatory drug indomethacin (IMC) on 1-hydroxyanthraquinone (1-HA)-induced carcinogenesis was investigated in a total of 69 male ACI/N rats. Animals in Group 1 were fed the diet containing 1.5% 1-HA for 48 weeks. The rats in Group 2 were given the 1-HA diet together with 16 ppm IMC in the drinking water for 48 weeks. Group 3 was given IMC alone throughout the study. Group 4 was served as an untreated control. At the end of the study, the incidences of large bowel and forestomach tumors in Group 2 were significantly smaller than those in Group 1 (large bowel tumors: 0/14 rats, 0% in Group 2 versus 12/27 rats, 44% in Group 1, p < 0.002; forestomach tumors: 2/14 rats, 14% in Group 2 versus 14/27 rats, 52% in Group 1, p < 0.01). Also, the incidences of inflammatory changes including ulcerative colitis and melanosis coli in colonic mucosa of rats of given 1-HA together with IMC were significantly reduced compared with those in rats given 1-HA alone (ulcerative colitis: 2/14 rats, 14% in Group 2 versus 20/27 rats, 74% in Group 1, p < 0.004). Concurrent administration of IMC with 1-HA caused a significant decrease in the bromodeoxyuridine labeling index of the colonic mucosa. These results indicate that the nonsteroidal anti-inflammatory drug IMC inhibits 1-HA-induced carcinogenesis and that this effect in decreasing the cell proliferation.
Tanaka
T
T
First Department of Pathology, Gifu University School of Medicine, Japan.
Suzui
M
M
Kojima
T
T
Okamoto
K
K
Wang
A
A
Mori
H
H
D000818:Animals; D000880:Anthraquinones / Q000633:toxicity*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D002273:Carcinogens / Q000633:toxicity*; D005770:Gastrointestinal Neoplasms / Q000139:chemically induced / Q000517:prevention & control*; D007213:Indomethacin / Q000627:therapeutic use*; D008297:Male; D065108:Ornithine Decarboxylase Inhibitors; D051381:Rats; D011912:Rats, Inbred ACI
D000880:Anthraquinones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D016588:Anticarcinogenic Agents; D002273:Carcinogens; D065108:Ornithine Decarboxylase Inhibitors; C061208:1-hydroxyanthraquinone; D007213:Indomethacin