Heflich R H, Neft R E
Division of Genetic Toxicology, National Center for Toxicological Research, Jefferson, AR 72079.
Mutat Res. 1994 Oct;318(2):73-114. doi: 10.1016/0165-1110(94)90025-6.
2-Acetylaminofluorene and 2-aminofluorene are among the most intensively studied of all chemical mutagens and carcinogens. Fundamental research findings concerning the metabolism of 2-acetylaminofluorene to electrophilic derivatives, the interaction of these derivatives with DNA, and the carcinogenic and mutagenic responses that are associated with the resulting DNA damage have formed the foundation upon which much of genetic toxicity testing is based. The parent compounds and their proximate and ultimate mutagenic and carcinogenic derivatives have been evaluated in a variety of prokaryotic and eukaryotic assays for mutagenesis and DNA damage. The reactive derivatives are active in virtually all systems, while 2-acetylaminofluorene and 2-aminofluorene are active in most systems that provide adequate metabolic activation. Knowledge of the structures of the DNA adducts formed by 2-acetylaminofluorene and 2-aminofluorene, the effects of the adducts on DNA conformation and synthesis, adduct distribution in tissues, cells and DNA, and adduct repair have been used to develop hypotheses to understand the genotoxic and carcinogenic effects of these compounds. Molecular analysis of mutations produced in cell-free, bacterial, in vitro mammalian, and intact animal systems have recently been used to extend these hypotheses.
2-乙酰氨基芴和2-氨基芴是所有化学诱变剂和致癌物中研究最为深入的物质。关于2-乙酰氨基芴代谢为亲电衍生物、这些衍生物与DNA的相互作用以及与由此产生的DNA损伤相关的致癌和诱变反应的基础研究结果，构成了许多遗传毒性测试的基础。母体化合物及其直接和最终的诱变和致癌衍生物已在各种原核和真核生物的诱变和DNA损伤试验中进行了评估。活性衍生物在几乎所有系统中都具有活性，而2-乙酰氨基芴和2-氨基芴在大多数能提供充分代谢活化作用的系统中具有活性。关于2-乙酰氨基芴和2-氨基芴形成的DNA加合物的结构、加合物对DNA构象和合成的影响、加合物在组织、细胞和DNA中的分布以及加合物修复的知识，已被用于提出假设，以了解这些化合物的遗传毒性和致癌作用。最近，对无细胞、细菌、体外哺乳动物和完整动物系统中产生突变的分子分析已被用于扩展这些假设。
