Eder E, Scheckenbach S, Deininger C, Hoffman C
Institut für Toxikologie, Universität Würzburg Germany.
Toxicol Lett. 1993 Apr;67(1-3):87-103. doi: 10.1016/0378-4274(93)90048-3.
alpha, beta-Unsaturated carbonyl compounds are industrially important compounds, ubiquitous in the environment and are formed endogenously. They interact with proteins and enzymes. Genotoxicity was found in eucaryotic cells and some compounds were carcinogenic. Unsaturated carbonyl compounds are considered to play an important role in human cancer. Insufficient and contradictory results were reported on mutagenicity. We demonstrated a clear mutagenic potential for these compounds and have shown interference of their bacterial toxicity with an adequate testing. Structure-mutagenicity relationships were confirmed by the results of the SOS-chromotest. The compounds induce DNA-strand breaks. However, we did not find indications for cross linking. With mutagenic alpha, beta-unsaturated carbonyl compounds we isolated and characterized 1,N2-cyclic deoxyguanosine adducts, 7,8-cyclic and 7-linear guanine adducts as well as 1,N2-7,8-biscyclic adducts and 1,N2-cyclic, 7-linear bisadducts. Reactivity of these compounds towards nucleosides runs in parallel with their mutagenic potential. Mutagenic and carcinogenic activities most probably depend on these reactions with DNA, and DNA adducts can be utilized as indicators for the role of these compounds in human carcinogenicity.
α,β-不饱和羰基化合物是工业上重要的化合物，在环境中普遍存在且可内源性形成。它们与蛋白质和酶相互作用。在真核细胞中发现了遗传毒性，一些化合物具有致癌性。不饱和羰基化合物被认为在人类癌症中起重要作用。关于致突变性的报道结果不足且相互矛盾。我们证明了这些化合物具有明显的致突变潜力，并通过适当的测试显示了它们对细菌毒性的干扰。SOS-显色试验结果证实了结构-致突变性的关系。这些化合物可诱导DNA链断裂。然而，我们未发现交联的迹象。对于具有致突变性的α,β-不饱和羰基化合物，我们分离并鉴定了1,N2-环化脱氧鸟苷加合物、7,8-环化和7-线性鸟嘌呤加合物以及1,N2-7,8-双环加合物和1,N2-环化、7-线性双加合物。这些化合物对核苷的反应性与其致突变潜力平行。致突变和致癌活性很可能取决于它们与DNA的这些反应，并且DNA加合物可作为这些化合物在人类致癌作用中所起作用的指标。
