In vivo formation and persistence of modified nucleosides resulting from alkylating agents

摘要: Alkylating agents are ubiquitous in the human environment and continuously synthesized vivo. Although many classes exist, interest has been focused on N-nitroso compounds, since mutagens for bacteria, phage, cells, carcinogens mammals. In contrast to aromatic amines polyaromatic hydrocarbons which can react at carbons, simple alkylating with nitrogens oxygens: 13 sites possible, including internucleotide phosphodiester. However, only Nnitroso compounds extensively oxygens. vivo, most possible derivatives have found after administration of methyl ethyl nitroso compounds. The ethylating more reactive toward oxygens than methylating carcinogenic terms total alkylation. This is true regardless whether or not require metabolic activation. It hypothesized that level persistence specific a "target" cell correlates oncogenesis. no single derivative be solely responsible this complex process, correlations cannot made even carcinogen acting various species types. Some chemically unstable, glycosyl bond broken (3- 7-alkylpurines), leaving apurinic may mutagenic. These, as well adducts, recognized by different enzymatic activities remove/ repair rates efficiencies depending number alkyl derivatives, enzyme content recognition enzyme. Evaluation exposure requires early sensitive methods detect initial damage extent each promutagenic adducts.