Chemoprevention of colon carcinogenesis by dietary administration of piroxicam, alpha-difluoromethylornithine, 16 alpha-fluoro-5-androsten-17-one, and ellagic acid individually and in combination.
Chemoprevention of colon carcinogenesis by dietary administration of piroxicam, alpha-difluoromethylornithine, 16 alpha-fluoro-5-androsten-17-one, and ellagic acid individually and in combination.
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发表时间：
1991
期刊：
影响因子：
11.2
通讯作者：
Chinthalapally;V. Rao;K. Tokumo;J. Rigotty;E. Zang;G. Kelloff;Bandaru S. Reddy
中科院分区：
文献类型：
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作者：
Chinthalapally;V. Rao;K. Tokumo;J. Rigotty;E. Zang;G. Kelloff;Bandaru S. Reddy
在雄性F344大鼠中研究了在氧化偶氮甲烷诱导的肠道肿瘤形成的启动和启动后阶段之前和期间，在饮食中单独和联合给予40%和80%最大耐受剂量（MTD）水平的吡罗昔康、D，L-alpha-二氟甲基鸟苷（DMFO）、16 α-氟-5-雄甾烯-17-酮（DHEA类似物8354）和鞣花酸（EA）的化学预防作用。在雄性F344大鼠中测定吡罗昔康、DFMO、DHEA类似物和EA的MTD水平，发现在改良AIN-76 A饲料中分别为500、5，000、500和10，000 ppm。当这些药物联合给药时，MTD水平为：吡罗昔康+DFMO，250和2500 ppm;吡罗昔康+DHEA类似物，250和250 ppm;吡罗昔康+EA，250和5000 ppm;吡罗昔康+DFMO + DHEA类似物，250、2500和250 ppm;吡罗昔康+DFMO + EA，250、2500和5000 ppm。根据这些MTD值，计算40%和80% MTD水平，并检测其疗效。在5周龄时，给动物喂食改良的AIN-76 A（对照）饮食和实验饮食，实验饮食含有40和80% MTD水平的吡罗昔康、DFMO、DHEA类似物和EA单独和组合。在7周龄时，除溶剂处理组外的所有动物均皮下给药。注射氧化偶氮甲烷（15 mg/kg体重/周，持续2周）。预期用于溶剂处理的动物接受s.c.注射等体积的生理盐水。在氧化偶氮甲烷和盐水处理后52周，对所有动物进行尸检，并在不同饮食组之间比较结肠和小肠肿瘤发生率（具有肿瘤的动物的百分比）和多样性（肿瘤/动物）。结果表明，40%和80% MTD水平的吡罗昔康和DFMO显著（P <0.001）抑制结肠和小肠肿瘤的发生率和多样性。DHEA类似物在40%MTD水平显著降低小肠和结肠肿瘤的发生率（P <0.05），而80%MTD的DHEA类似物仅抑制小肠肿瘤的发生。电针40%和80% MTD对结肠癌的发生率无显著影响（P> 0.05），而电针80% MTD对小肠腺癌的发生率有显著抑制作用（P <0.01）。在联合研究中，与对照饲料喂养动物的结肠腺癌发生率（72.2%）和多重性（1.14 +/- 0.18）相比，40%和80% MTD水平的吡罗昔康+DFMO显著（P <0.001）抑制结肠腺癌发生率（8.3%）和多重性（0.08 +/- 0.04）（SE）。（400字处截断摘要）
The chemopreventive action of 40 and 80% maximum tolerated dose (MTD) levels of piroxicam, D,L-alpha-difluoromethylornithine (DMFO), 16 alpha-fluoro-5-androsten-17-one (DHEA analogue 8354), and ellagic acid (EA) administered in diet individually and in combination before and during initiation and postinitiation phases of azoxymethane-induced neoplasia of the intestine was studied in male F344 rats. The MTD levels of piroxicam, DFMO, DHEA analogue, and EA were determined in male F344 rats and found to be 500, 5,000, 500, and 10,000 ppm, respectively, in modified AIN-76A diet. When these agents were fed in combination, the MTD levels were: piroxicam plus DFMO, 250 and 2500 ppm; piroxicam plus DHEA analogue, 250 and 250 ppm; piroxicam plus EA, 250 and 5000 ppm; piroxicam plus DFMO plus DHEA analogue, 250, 2500, and 250 ppm; and piroxicam plus DFMO plus EA, 250, 2500, and 5000 ppm. From these MTD values, 40 and 80% MTD levels were calculated and tested for their efficacy. At 5 weeks of age, animals were fed the modified AIN-76A (control) diet and experimental diets containing 40 and 80% MTD levels of piroxicam, DFMO, DHEA analogue, and EA individually and in combination. At 7 weeks of age, all animals except the vehicle-treated groups were administrated s.c. injections of azoxymethane (15 mg/kg body weight/week for 2 weeks). Animals intended for vehicle treatment received s.c. injections of an equal volume of normal saline. Fifty-two weeks after azoxymethane and saline treatment all the animals were necropsied, and colon and small intestinal tumor incidence (percentage of animals with tumors) and multiplicity (tumors/animal) were compared among various dietary groups. The results indicate that 40 and 80% MTD levels of dietary piroxicam and DFMO significantly (P less than 0.001) inhibited colon and small intestinal tumor incidence and multiplicity. DHEA analogue at 40% MTD level significantly decreased the small intestinal and colon tumor incidences (P less than 0.05), whereas 80% MTD of DHEA analogue inhibited only small intestinal tumor incidence. EA at 40 and 80% MTDs had no significant effect on colon tumor incidence (P greater than 0.05), but 80% MTD of EA showed a significant inhibitory effect on the incidence of small intestinal adenocarcinomas (P less than 0.01). In the combination study, 40 and 80% MTD levels of piroxicam plus DFMO significantly (P less than 0.001) inhibited colon adenocarcinoma incidence (8.3%) and multiplicity (0.08 +/- 0.04) (SE) when compared to colon adenocarcinoma incidence (72.2%) and multiplicity (1.14 +/- 0.18) in control diet-fed animals.(ABSTRACT TRUNCATED AT 400 WORDS)