Brouns R M, Bos R P, Van Doorn R, Henderson P T
Toxicology. 1982;23(2-3):235-47. doi: 10.1016/0300-483x(82)90101-9.
Isolated rat liver cells were shown to metabolize the aromatic amine benzidine to reactive products which are mutagenic to Salmonella typhimurium TA 1538 and which give rise to DNA excision repair within the liver cells. Intact rat liver cells are shown to be more active in the formation of mutagenic metabolites than the 9000-g supernatant from these cells. Data are presented which are in favour of the role of N-acetylation in this respect. Furthermore, indications are presented that a sulfation reaction is involved in the generation of DNA modifying metabolites, whereas formation of mutagenic products is likely to proceed via deacetylation and/or N,O-acyltransfer. Finally, data are given about the extrahepatocellular appearance of premutagenic metabolites which are more prone to metabolic activation by additional metabolic factors in the Salmonella assay than benzidine itself. The impact of these observations on the estimation of the genotoxic potential of benzidine will be discussed.
已证明分离的大鼠肝细胞能将芳香胺联苯胺代谢为对鼠伤寒沙门氏菌TA 1538具有致突变性的反应产物，并且这些产物会在肝细胞内引发DNA切除修复。完整的大鼠肝细胞在形成致突变性代谢产物方面比这些细胞的9000g上清液更具活性。给出的数据支持N - 乙酰化在这方面的作用。此外，有迹象表明硫酸化反应参与了DNA修饰代谢产物的生成，而致突变产物的形成可能通过脱乙酰化和/或N,O - 酰基转移进行。最后，给出了关于前致突变代谢产物在肝外出现的数据，这些代谢产物在沙门氏菌试验中比联苯胺本身更容易受到其他代谢因子的代谢激活。将讨论这些观察结果对联苯胺遗传毒性潜力评估的影响。
