PREVENTION BY CHEMOPREVENTIVE AGENTS OF AZOXYMETHANE-INDUCED FOCI OF ABERRANT CRYPTS IN RAT COLON
PREVENTION BY CHEMOPREVENTIVE AGENTS OF AZOXYMETHANE-INDUCED FOCI OF ABERRANT CRYPTS IN RAT COLON
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DOI：
10.1016/0304-3835(91)90073-q
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发表时间：
1991-12-09
期刊：
影响因子：
9.7
通讯作者：
KHOURY, MD
中科院分区：
文献类型：
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作者：
PEREIRA, MA;KHOURY, MD
异常隐窝病灶是假定的结肠癌癌前病变，可以在用亚甲蓝染色的未切片结肠中检测到。评估了该测定证明化学预防活性的能力。雄性 Sprague-Dawley 大鼠间隔 1 周接受两次皮下注射，每次 15 mg/kg 氧化偶氮甲烷。动物在第一次注射氧化偶氮甲烷前1周开始在饮食中接受测试剂，并持续直至5周后处死。氧化偶氮甲烷处理诱导的异常隐窝病灶数量从不使用任何化学预防剂的228病灶/动物减少到N-乙酰半胱氨酸处理后的151病灶/动物；通过脱氢表雄酮对 121 个病灶/动物进行治疗；由α-二氟甲基鸟氨酸至161；并通过1，2-氧代噻唑烷-4-羧酸酯变为121。其他试剂（二烯丙基硫醚、鞣花酸和异硫氰酸苯乙酯）没有显着改变氧化偶氮甲烷诱导的病灶/动物的数量。未接受氧化偶氮甲烷的动物平均有 0.72 个病灶/动物。我们的结果表明，四种测试的药物可能会减少氧化偶氮甲烷诱发的结肠癌，这需要证实。有必要在结肠测定中进一步验证异常隐窝的病灶，以筛选化学预防剂的化学物质。
Foci of aberrant crypts are putative preneoplastic lesions of colon cancer that can be detected in unsectioned colons stained with methylene blue. The ability of this assay to demonstrate chemopreventive activity was evaluated. Male Sprague-Dawley rats received two subcutaneous injections 1 week apart, of 15 mg/kg azoxymethane each. The animals started to receive the test agents in their diet 1 week prior to the first injection of azoxymethane and continuously until killed 5 weeks later. The number of foci of aberrant crypts induced by the treatment of azoxymethane was reduced from 228 foci/animal without any chemopreventive agent to 151 foci/animal by N-acetylcysteine; to 121 foci/animal by dehydroepiandrosterone; to 161 by alpha-difluoromethylornithine; and to 121 by 1,2-oxothiazolidine-4-carboxylate. The other agents (diallyl sulfide, ellagic acid and phenethyl isothiocyanate) did not significantly alter the number of foci/animal induced by azoxymethane. Animals that did not receive azoxymethane had an average of 0.72 foci/animal. Our results suggest that four of the tested agents might reduce azoxymethane-induced colon cancer, which requires confirmation. Further validation of the foci of aberrant crypt in the colon assay to screen chemicals for chemoprevention agents is warranted.