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[-14C]黄曲霉毒素B1与大鼠和仓鼠细胞大分子的结合

Binding of [-14C]aflatoxin B1 to cellular macromolecules in the rat and hamster.

作者信息

Garner R C, Wright C M

出版信息

Chem Biol Interact. 1975 Aug;11(2):121-31. doi: 10.1016/0009-2797(75)90019-8.

DOI:10.1016/0009-2797(75)90019-8
PMID:1139740
Abstract

The uptake and binding of ring-labelled [-14C]aflatoxin B1 (AFB1) by rat and hamster liver and kidney has been studied, the former species being extremely sensitive to the carcinogenic action of AFB, whereas the latter is resistant. In contrast to an earlier report (Lijinsky et al, Cancer Res., 30 (1970) 2280-2283, binding of the carcinogen to nucleic acids was far greater than that to protein. Rat liver DNA bound ten times and rRNA twenty times more carcinogen than protein. There were also differences in the amount of carcinogen bound to rat liver nucleic acids compared to those of the hamster, the latter species binding lower amounts of the carcinogen. Rat liver DNA bound four times and rRNA ten times as much AFB1 6 h after carcinogen administration whereas liver protein bound AFB1 was similar for the two species. Not only was there a difference in the amount of AFB1 bound but whereas in the rat, liver nucleic acid bound carcinogen decayed with time, no such fall was seen in the hamster, this remaining at a low level throughout the 48-h time period studied. In contrast, reaction of the carcinogen with kidney macromolecules was similar for the two species. The much higher binding of AFB1 to nucleic acids than to protein might account for the potent carcinogenicity of this compound in the rat, particularly since liver protein binding does not differ between a susceptible and a resistant species. A further important factor in determining carcinogenic sensitivity may be the removal of nucleic acid bound radioactivity with time, a possible repair process.

摘要

研究了环标记的[-14C]黄曲霉毒素B1(AFB1)在大鼠和仓鼠肝脏及肾脏中的摄取和结合情况,大鼠对AFB的致癌作用极为敏感,而仓鼠则具有抗性。与早期报告(Lijinsky等人,《癌症研究》,30(1970)2280 - 2283)相反,致癌物与核酸的结合远大于与蛋白质的结合。大鼠肝脏DNA结合的致癌物是蛋白质的十倍,rRNA是二十倍。与仓鼠相比,大鼠肝脏核酸结合的致癌物量也存在差异,仓鼠结合的致癌物量较低。给予致癌物6小时后,大鼠肝脏DNA结合的AFB1是蛋白质的四倍,rRNA是十倍,而两种动物肝脏蛋白质结合的AFB1相似。不仅AFB1结合量存在差异,而且在大鼠中,肝脏核酸结合的致癌物随时间衰减,而在仓鼠中未观察到这种下降,在整个48小时的研究时间段内其一直保持在低水平。相比之下,两种动物致癌物与肾脏大分子的反应相似。AFB1与核酸的结合远高于与蛋白质的结合,这可能解释了该化合物在大鼠中的强致癌性,特别是因为敏感和抗性物种之间肝脏蛋白质结合没有差异。决定致癌敏感性的另一个重要因素可能是随着时间推移核酸结合放射性的去除,这可能是一个修复过程。

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Binding of [-14C]aflatoxin B1 to cellular macromolecules in the rat and hamster.[-14C]黄曲霉毒素B1与大鼠和仓鼠细胞大分子的结合
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Aflatoxin B1 mutagenesis, DNA binding, and adduct formation in Salmonella typhimurium.黄曲霉毒素B1在鼠伤寒沙门氏菌中的诱变、DNA结合及加合物形成
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Identification of the principal aflatoxin B1-DNA adduct formed in vivo in rat liver.大鼠肝脏中体内形成的主要黄曲霉毒素B1-DNA加合物的鉴定。
Proc Natl Acad Sci U S A. 1978 Apr;75(4):1745-9. doi: 10.1073/pnas.75.4.1745.
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Structural identification of the major DNA adduct formed by aflatoxin B1 in vitro.黄曲霉毒素B1体外形成的主要DNA加合物的结构鉴定。
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