CHEMOPREVENTION OF THE NATURALLY-OCCURRING CARCINOGEN 1-HYDROXYANTHRAQUINONE-INDUCED CARCINOGENESIS BY THE NONSTEROIDAL ANTIINFLAMMATORY DRUG INDOMETHACIN IN RATS

The chemopreventive effect of the nonsteroidal anti-inflammatory drug indomethacin (IMC) on 1-hydroxyanthraquinone (1-HA)-induced carcinogen esis was investigated in a total of 69 male ACI/N rats. Animals in Gro up 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 drink ing water for 48 weeks. Group 3 was given IMC alone throughout the stu dy. Group 4 was served as an untreated control. At the end of the stud y, the incidences of large bowel and forestomach tumors in Group 2 wer e significantly smaller than those in Group 1 (large bowel tumors: 0/1 4 rats, 0% in Group 2 versus 12/27 rats, 44% in Group 1, p < 0.002; fo restomach 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 inclu ding ulcerative colitis and melanosis coli in colonic mucosa of rats o f given I-HA together with IMC were significantly reduced compared wit h those in rats given 1-HA alone (ulcerative colitis: 2/14 rats, 14% i n Group 2 versus 20/27 rats, 74% in Group 1, p < 0.004). Concurrent ad ministration of IMC with 1-HA caused a significant decrease in the bro modeoxyuridine labeling index of the colonic mucosa. These results ind icate that the nonsteroidal anti-inflammatory drug IMC inhibits I-HA-i nduced carcinogenesis and that this effect may be related to its effec t in decreasing the cell proliferation.