AFLATOXIN-B1 BINDING TO PLASMA-ALBUMIN AND LIVER DNA UPON CHRONIC ADMINISTRATION TO RATS
AFLATOXIN-B1 BINDING TO PLASMA-ALBUMIN AND LIVER DNA UPON CHRONIC ADMINISTRATION TO RATS
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DOI：
10.1093/carcin/7.6.853
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发表时间：
1986-06-01
期刊：
影响因子：
4.7
通讯作者：
TURSI, F
中科院分区：
文献类型：
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作者：
WILD, CP;GARNER, RC;TURSI, F
用单次或多次经口灌胃给予雄性Wistar大鼠肝癌原黄曲霉毒素B_1（AFB_1），测定其与血浆蛋白和肝DNA的结合率。在单次剂量（3.5-200 μ g/kg AFB 1）后24小时，发现与血浆蛋白结合的黄曲霉毒素水平和与肝DNA结合的黄曲霉毒素水平之间的恒定比率。总计0.98 .+-。在该时间点，2.15%的给药剂量与血浆蛋白结合。在慢性研究中，大鼠每天接受两次剂量的0.5 μ g AFB 1，并在第2、3、7、14、21和24天处死动物组。黄曲霉毒素与血浆蛋白的结合累积到比单次给药后高3倍的水平。结合水平在处理的第7天和第14天之间达到平台，然后保持稳定直到实验结束。与DNA的结合也积累了2.5倍，与血浆蛋白平行，在处理的第7天和第14天之间结合达到平台。在慢性和急性研究中，通过Sephadex G-200色谱分离血浆蛋白表明，所有可检测到的结合黄曲霉毒素均与对应于白蛋白的单峰相关。因此，观察到一个恒定的比例，慢性或单次暴露后，血浆白蛋白结合黄曲霉毒素的浓度和结合到DNA的肝脏，致癌的靶器官黄曲霉毒素1。为了研究AFB 1在人类原发性肝细胞癌病因学中的作用，有一种在个体水平上评估人类长期暴露的方法将具有重要价值。本文中提出的意见的相关性进行了讨论，根据这样的要求。
The hepatocarcinogen aflatoxin B1 (AFB1) was administered to male Wistar rats by oral intubation in either single or repeated doses and the binding to plasma protein and liver DNA determined. Twenty-four hours after a single dose (3.5-200 .mu.g/kg AFB1) a constant ratio was found between levels of aflatoxin bound to plasma protein and that bound to liver DNA. In total 0.98 .+-. 2.15% of the administered dose was bound to the plasma protein at this time point. In the chronic study rats received two doses of 0.5 .mu.g AFB1/day and groups of animals were killed on days 2, 3, 7, 14, 21 and 24. Binding of aflatoxin to plasma protein accumulated to a level 3-fold higher than that seen after a single dose. Levels of binding reached a plateau between days 7 and 14 of treatment and then remained stable until the end of the experiment. Binding to DNA also accumulated, 2.5-fold and in parallel to plasma protein, binding reached a plateau between days 7 and 14 of treatment. In both the chronic and acute studies fractionation of the plasma proteins by Sephadex G-200 chromatography showed that all detectable bound aflatoxin was associated with a single peak corresponding to albumin. Thus, a constant ratio was observed, after chronic or single exposure, between the concentration of plasma albumin-bound aflatoxin and that bound to DNA of the liver, the target organ for carcinogenesis by AFB1. In order to investigate the proposed role of AFB1 in the aetiology of primary hepatocellular carcinoma in man it would be of great value to have a method for assessing long-term human exposure at an individual level. The relevance of the observations presented in this paper are discussed in the light of such a requirement.