The activation of aflatoxin B1 in liver slices and in bacterial mutagenicity assays using livers from different species including man.
The activation of aflatoxin B1 in liver slices and in bacterial mutagenicity assays using livers from different species including man.
复制标题
使用来自不同物种（包括人类）的肝脏进行肝脏切片和细菌致突变性测定中黄曲霉毒素 B1 的激活。
DOI：
10.1093/carcin/2.10.1063
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发表时间：
1981
期刊：
影响因子：
4.7
通讯作者：
Norpoth,K
中科院分区：
文献类型：
--
作者：
Booth,SC;Bösenberg,H;Garner,RC;Hertzog,PJ;Norpoth,K
在两种体外系统中比较了黄曲霉毒素B_1（AFB_1）的激活作用：（1）与[~（14）C]或[~ 3 H] AFB_1孵育的肝片中DNA的结合;（2）用9000 × g未诱导肝的上清液（S-9）进行激活的标准细菌突变系统。研究了影响黄曲霉毒素致癌作用的几个因素，即种属、性别、苯巴比妥预处理和黄曲霉毒素G1（AFG 1）与AFB 1的比较。肝片DNA结合率的变化趋势为：大鼠>仓鼠>小鼠，对照组>苯巴比妥预处理大鼠，AFB_1> AFG_1。这一趋势的一个例外是在雄性和雌性大鼠肝脏中发现的结合水平相似，后者对AFB 1致癌作用的敏感性较低。这一结果表明，AFB 1致癌性的性别差异可能是由于损伤修复或致癌促进阶段的差异。[~ 3 H] AFB_1与新鲜人肝组织DNA切片的结合水平在6个样品之间有相当大的差异。数值范围为0.7-8.5 ng AFB 1/mg DNA，介于仓鼠和小鼠中观察到的数值之间。致突变性数据与种属差异（仓鼠>大鼠>小鼠）或苯巴比妥预处理相关的致癌性无关。添加谷胱甘肽和/或S-9、AFB 1和辅助因子预孵育顶层琼脂混合物并不能改善这种相关性。然而，预计这两种系统之间的差异是由于致突变性试验中代谢系统的限制，而不是DNA结合或细菌突变是更有效的终点。
The activation of aflatoxin B1(AFB1) has been compared in twoin vitrosystems: (1) binding to DNA in liver slices incubated with [14C] or [3H]AFB1; (2) standard bacterial mutation systems using 9000 x g supernatant (S-9) fractions from uninduced livers for activation. Several factors which modify aflatoxin carcinogenesis were investigated, namely species, sex, phenobarbitone pretreatment and aflatoxin G1(AFG1) compared with AFB1. The results from DNA binding in liver slices showed the following trends: rat > hamster > mouse, control > phenobarbitone-pretreated rat and AFB1> AFG1which correlated directly with trends in carcinoenicity. An exception to this trend was the similar level of binding found in male and female rat livers, the latter being less susceptible to AFB1carcinogenesis. This result suggests that sex differences in AFB1carcinogenicity may be due to differences in repair of lesions or during the promotion phase of carcinogenesis. The levels of binding of [3H]AFB1to DNA slices from fresh human liver biopsies showed considerable variation between the six samples. Values ranged from 0.7–8.5 ng AFB1/mg DNA, which are in between values observed in the hamster and mouse. Mutagenicity data did not correlate with carcinogenicity in relation to species differences (hamster > rat > mouse) nor phenobarbitone pretreatment. Supplementation of the top agar mixture with glutathione and/or pre-incubation of S-9, AFB1and cofactors did not improve this correlation. Nevertheless, it is expected that differences between these two systems are due to limitations of the metabolizing system in mutagenicity tests, rather than either DNA binding or bacterial mutation being the more valid end point.