INHIBITION OF COLON CARCINOGENESIS BY PROSTAGLANDIN SYNTHESIS INHIBITORS AND RELATED-COMPOUNDS

被引:145
作者
REDDY, BS [1 ]
TOKUMO, K [1 ]
KULKARNI, N [1 ]
ALIGIA, C [1 ]
KELLOFF, G [1 ]
机构
[1] NCI,DIV CANC CONTROL & PREVENT,CHEMOPREVENT BRANCH,BETHESDA,MD 20856
关键词
D O I
10.1093/carcin/13.6.1019
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The inhibitory effect of 40 and 80% maximum tolerated dose (MTD) levels of piroxicam, ibuprofen, ketoprofen and glycyrrhetinic acid on colon carcinogenesis was investigated in male F344 rats. The MTD levels of piroxicam, ibuprofen, ketoprofen and glycyrrhetinic acid as determined in male F344 rats were 500, 500, 250 and 3000 p.p.m. respectively. At 5 weeks of age, groups of male F344 rats were fed the control (AIN-76A) diet and 40 and 80% MTD levels of each test agent in AIN-76A diet. At 7 weeks of age, all animals except the vehicle (saline)-treated controls received azoxy-methane (AOM) at a dose rate of 15 mg/kg body wt, once weekly for 2 weeks. All animals were necropsied 50 weeks after the second AOM injection and colon tumor incidences were compared among the groups fed the control diet and chemopreventive agents. Animals fed 400 (80% MTD) and 200 p.p.m. (40% MTD) of piroxicam, 400 p.p.m. (80% MTD) of ibuprofen and 200 p.p.m. (80% MTD) of ketoprofen showed a significant inhibition of colon tumorigenesis as compared to those fed the control diet. Results analyzed by the linear regression method suggested a dose-dependent inhibition of colon carcinogenesis with increasing levels of piroxicam or ibuprofen. In contrast, glycyrrhetinic acid had no measurable chemopreventive effect on colon carcinogenesis.
引用
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页码:1019 / 1023
页数:5
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