去甲哈尔满对大鼠肝脏微粒体体外代谢苯并[a]芘的影响及其对苯并[a]芘致突变性的增强作用。

The effect of norharman on the metabolism of benzo[alpha]pyrene by rat-liver microsomes in vitro in relation to its enhancement of the mutagenicity of benzo[alpha]pyrene.

作者信息

Fujino T, Fujiki H, Nagao M, Yahagi T, Seino Y, Sugimura T

出版信息

Mutat Res. 1978 Nov;58(2-3):151-8. doi: 10.1016/0165-1218(78)90004-6.

Abstract

The effect of norharman on the metabolism of benzo[alpha]pyrene by rat-liver microsomes was studied. Separation of the metabolites into hydrophilic and hydrophobic fractions showed that norharman inhibited the conversion of hydrophobic metabolites to hydrophilic ones. Analysis of the hydrophobic metabolites by high-pressure liquid chromatography showed that norharman also inhibited the disappearance of benzo[alpha]pyrene itself. However, large amounts of hydrophobic metabolites, such as phenol, quinones and diols, were formed in the presence of norharman, and formation of the strong mutagen 7,8-dihydroxybenzo[alpha]pyrene was increased 10-fold by norharman. The increase in formation of this compound may be one of the chief reasons why norharman enhances the mutagenicity of benzo[alpha]pyrene on Salmonella typhimurium.

摘要

研究了去甲哈尔满对大鼠肝脏微粒体代谢苯并[a]芘的影响。将代谢产物分离成亲水和疏水部分表明，去甲哈尔满抑制疏水代谢产物向亲水代谢产物的转化。通过高压液相色谱分析疏水代谢产物表明，去甲哈尔满还抑制苯并[a]芘本身的消失。然而，在去甲哈尔满存在的情况下会形成大量疏水代谢产物，如苯酚、醌和二醇，并且去甲哈尔满使强诱变剂7,8-二羟基苯并[a]芘的形成增加了10倍。该化合物形成的增加可能是去甲哈尔满增强苯并[a]芘对鼠伤寒沙门氏菌致突变性的主要原因之一。