Carcinogenicity of aflatoxicol in Fischer 344 rats.
Carcinogenicity of aflatoxicol in Fischer 344 rats.
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黄曲霉毒素对 Fischer 344 大鼠的致癌性。
DOI：
10.1093/jnci/66.6.1159
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发表时间：
1981
期刊：
影响因子：
--
通讯作者：
Sinnhuber,RO
中科院分区：
文献类型：
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作者：
Nixon,JE;Hendricks,JD;Pawloswki,NE;Loveland,PM;Sinnhuber,RO
阿瓦托毒素(AFL)是黄曲霉毒素B1(AFB1)的代谢物，由包括人类在内的几个物种的肝脏制剂在体外形成。物种对黄曲霉毒素F1的敏感性与该物种将黄曲霉毒素F1代谢为AFL的能力呈正相关。因此，将AFB1转化为AFL是一个值得怀疑的解毒步骤。用化学方法从黄曲霉毒素1制备的AFL的非对映异构体混合物，通过测定4组20只断奶雄性F344大鼠的肿瘤发病率来比较AFL的致癌活性。4组大鼠分别饲喂不含黄曲霉毒素的阴性对照饲料、阳性50 ppb的AFB1对照饲料、50 ppb的AFL饲料或200 ppb的AFL饲料，为期1年，然后在第2年结束时被处死。肝细胞癌的发生率分别为0、40、20和70%，表明AFL在大鼠体内具有致癌性。数据显示，AFL的非对映异构体混合物的致癌性是AFB1的一半，而且剂量反应几乎是线性的，因为剂量增加四倍会导致肿瘤发病率增加3.5倍。这些数据没有明确地证明AFL是一种近似性致癌物质，但AFB1到AFL的代谢不应被认为是有效的解毒反应。
Aflatoxicol (AFL), a metabolite of aflatoxin B1(AFB1), is formed in vitro by liver preparations from several species including humans. A positive correlation appears to exist between the sensitivity of a species to AFB1and the species' ability to metabolize AFB1to AFL. Conversion of AFB1to AFL is, therefore, a questionable detoxification step. The carcinogenicity of a diastereoisomeric mixture of AFL, prepared chemically from AFB1, was compared to AFB1by tumor incidences being determined in 4 groups of 20 weanling male F344 rats fed either a negative control diet with no aflatoxin, a positive 50-ppb AFB1 control diet, a 50-ppb AFL diet, or a 200-ppb AFL diet for 1 year and then killed at the end of the 2d year. The respective hepatocellular carcinoma incidences were 0, 40, 20, and 70%, demonstrating that AFL is carcinogenic in the rat. The data show that a diastereoisomeric mixture of AFL is one-half as carcinogenic as AFB1 , and the dose response appeared nearly linear in that a fourfold increase in dose produced a 3.5-fold increase in tumor incidence. The data did not establish unequivocally that AFL is a proximate carcinogen, but metabolism of AFB1to AFL should not be considered an efficient detoxification reaction.