Razzouk C, Roberfroid M
Toxicol Lett. 1983 May;16(3-4):339-45. doi: 10.1016/0378-4274(83)90196-0.
As compared to rat liver microsomal arylamide N-hydroxylase both the dog and the human enzymes have lower affinity but higher activity. SKF525A, a well known effector of cytochrome P-450 dependent mixed function oxidases, activates the hepatic N-hydroxylase of all three species. This effect is concentration dependent and tends to plateau at 50 X 10(-6)M. As previously demonstrated with rat liver microsomes, the ring-hydroxylated, non-toxic, metabolites of 2-acetylaminofluorene, interact with the N-hydroxylating enzyme. These interactions are both compound- and species-specific. The most striking differences are seen with the paraphenolic product which activates the rat, does not affect the dog and inhibits the human liver enzyme. In the liver of this last species, that compound is the main metabolite of 2-acetylaminofluorene (2-AAF).
与大鼠肝脏微粒体芳基酰胺N-羟化酶相比，犬和人的酶具有较低的亲和力但较高的活性。SKF525A是一种著名的细胞色素P-450依赖性混合功能氧化酶效应剂，可激活所有这三个物种的肝脏N-羟化酶。这种效应是浓度依赖性的，在50×10⁻⁶M时趋于平稳。如先前在大鼠肝脏微粒体中所证实的，2-乙酰氨基芴的环羟基化、无毒代谢物与N-羟化酶相互作用。这些相互作用具有化合物特异性和物种特异性。对位酚类产物的差异最为显著，它可激活大鼠的酶，对犬的酶无影响，却抑制人肝脏的酶。在最后一个物种的肝脏中，该化合物是2-乙酰氨基芴（2-AAF）的主要代谢物。
