Neumann H G
Recent Results Cancer Res. 1983;84:77-89. doi: 10.1007/978-3-642-81947-6_5.
The initial step in tumor formation with aromatic amines is assumed to involve the modification of nucleic acids. Reactive metabolites bind covalently to purine and pyrimidine bases. The extent of formation of DNA adducts and their persistence is therefore expected to correlate with the biological effect. Using [3H]trans-4-amino-stilbene derivatives as model compounds, several parameters have been measured in susceptible and nonsusceptible rat tissues: total initial DNA binding, initial pattern of adducts, persistence of DNA adducts, accumulation of DNA binding after repeated doses, and persistence of DNA adducts after repeated doses. They did not correlate with tissue susceptibility. The tissue burden decreased in the order: liver greater than kidney greater than lung greater than glandular stomach greater than Zymbal gland. The latter tissue is the primary target for tumor formation. Comparison with other aromatic amines shows that aminostilbene derivatives are no exceptions. The role of specific nucleic acid modifications for mutagenic and carcinogenic effects is also difficult to evaluate in these cases. It is therefore emphasized that modulation of secondary steps in the multistage process may largely influence the final outcome. The role of cell proliferation and its stimulation as well as tumor promoting effects are discussed. Aminostilbene derivatives appear to produce primary lesions quite efficiently in rat liver but lack cytotoxic and promoting properties for this tissue.
芳香胺导致肿瘤形成的初始步骤被认为涉及核酸的修饰。活性代谢产物与嘌呤和嘧啶碱基共价结合。因此，DNA加合物的形成程度及其持久性预计与生物学效应相关。使用[3H]反式-4-氨基芪衍生物作为模型化合物，在易感和不易感的大鼠组织中测量了几个参数：总的初始DNA结合、加合物的初始模式、DNA加合物的持久性、重复给药后DNA结合的积累以及重复给药后DNA加合物的持久性。它们与组织易感性无关。组织负荷按以下顺序降低：肝脏大于肾脏大于肺大于腺胃大于齐默尔腺。后一种组织是肿瘤形成的主要靶器官。与其他芳香胺的比较表明，氨基芪衍生物也不例外。在这些情况下，特定核酸修饰对诱变和致癌作用的作用也难以评估。因此强调，多阶段过程中二级步骤的调节可能在很大程度上影响最终结果。讨论了细胞增殖及其刺激的作用以及肿瘤促进作用。氨基芪衍生物似乎能在大鼠肝脏中相当有效地产生原发性损伤，但对该组织缺乏细胞毒性和促进作用。
