Morishita Y, Yoshimi N, Kawabata K, Matsunaga K, Sugie S, Tanaka T, Mori H
First Department of Pathology, Gifu University School of Medicine.
Jpn J Cancer Res. 1997 Sep;88(9):815-20. doi: 10.1111/j.1349-7006.1997.tb00456.x.
Regressive effects of four chemopreventive agents [5-hydroxy-4-(2-phenyl-(E)-ethenyl)-2(5H)-furanone (KYN-54), S-methyl methanethiosulfonate (MMTS), chlorogenic acid (CA), and piroxicam] on azoxymethane (AOM)-induced aberrant crypt foci (ACF) in the colon of male F344 rats were examined by dietary exposure. At six weeks of age, 60 rats of groups 1 through 5 received subcutaneous injections of AOM (15 mg/kg body weight) once a weeks. Twelve weeks after the first carcinogen injection, when the occurrence of ACF was maximal, the rats in groups 2 through 5 were started on diet containing the test chemicals as follows: group 2, KYN-54 (0.02%); group 3, MMTS (0.01%); group 4, CA (0.025%); and group 5, piroxicam (0.0125%). Group 1 (20 rats) was kept on the basal diet alone, and group 6 (12 rats) served as an untreated control. Rats in each group were killed at 6, 12, 18, or 24 weeks after the start of the experiment, and the yield of ACF in the colon of each group at 18 or 24 weeks was compared with that at 12 weeks. The number of ACF per rat colon of each group at 18 or 24 weeks was smaller than that at 12 weeks. The reduction rates at 18 weeks were 7% in group 1 (AOM alone), 11% in group 2 (AOM + KYN-54), 10% in group 3 (AOM + MMTS), 51% in group 4 (AOM + CA) (P < 0.01), and 33% in group 5 (AOM + piroxicam) (P < 0.02), while at 24 weeks they were 12%, 26%, 51% (P < 0.002), 43% (P < 0.05), and 70% (P < 0.001), respectively. These results indicate that chemopreventive agents for large bowel carcinogenesis, i.e., KYN-54, MMTS, CA, and piroxicam, are not only able to prevent the development of ACF, but also can regress ACF, which are regarded as precursor lesions of colorectal cancer.
通过饮食暴露，研究了四种化学预防剂[5-羟基-4-(2-苯基-(E)-乙烯基)-2(5H)-呋喃酮（KYN-54）、甲硫基甲烷磺酸盐（MMTS）、绿原酸（CA）和吡罗昔康]对雄性F344大鼠结肠中由偶氮甲烷（AOM）诱导的异常隐窝灶（ACF）的消退作用。6周龄时，第1组至第5组的60只大鼠每周皮下注射一次AOM（15mg/kg体重）。在首次注射致癌物12周后，当ACF的发生率最高时，第2组至第5组的大鼠开始食用含有以下受试化学物质的饲料：第2组，KYN-54（0.02%）；第3组，MMTS（0.01%）；第4组，CA（0.025%）；第5组，吡罗昔康（0.0125%）。第1组（20只大鼠）仅喂食基础饲料，第6组（12只大鼠）作为未处理对照。在实验开始后的6、12、18或24周处死每组大鼠，并将每组在18或24周时结肠中ACF的产量与12周时的产量进行比较。每组大鼠结肠在18或24周时的ACF数量均少于12周时。第1组（仅AOM）在18周时的减少率为7%，第2组（AOM + KYN-54）为11%，第3组（AOM + MMTS）为10%，第4组（AOM + CA）为51%（P < 0.01），第5组（AOM + 吡罗昔康）为33%（P < 0.02）；而在24周时，它们分别为12%、26%、51%（P < 0.002）、43%（P < 0.05）和70%（P < 0.001）。这些结果表明，用于预防大肠癌的化学预防剂，即KYN-54、MMTS、CA和吡罗昔康，不仅能够预防ACF的发生，而且还能使ACF消退，而ACF被视为结直肠癌的前体病变。
