title: Reactivity and genotoxicity of arylnitrenium ions in bacterial and mammalian cells.
abstract: Electrophilic arylnitrenium ions are considered to be the ultimate reactive intermediates formed by metabolism of mutagenic and carcinogenic arylamines and nitroarenes; they can produce DNA damage by reaction with specific sites on DNA bases. We studied their formation, reactivity and the genotoxic sequelae of their reactions with cellular DNA to understand the mutagenic and carcinogenic activities of arylamines and nitroarenes as a function of their chemical structure. Arylnitrenium ions were generated by the convenient non-metabolic procedure, photolysis of arylazides, to study the reactivity of these ultimate intermediates with DNA, by means of 32P-postlabelling, and the induction of histidine reversions in Salmonella, HPRT mutations and sister chromatid exchange in mammalian (Chinese hamster V79) cells. Good correlations were observed between the DNA-binding potencies and the mutagenic and SCE-inducing potencies of the arylnitrenium ions, among these the nitrenium ions derived from the heterocyclic food mutagens/carcinogens MeIQ, IQ, and MeIQx. This suggests that the reactivity of the arylnitrenium ions and the quantity of adducts formed with DNA are the principal determinants of the final quantity of genetic alterations in Salmonella and in V79 cells. Conversely, the quality of the adducts, that is, the structure of the arylamine residue bound, appears to be of less significance.
authors.affiliation: Institut für Toxikologie, Universität Würzburg, Germany.
authors.forename: R S
authors.initials: RS
authors.lastname: Kerdar
authors.forename: D
authors.initials: D
authors.lastname: Dehner
authors.forename: D
authors.initials: D
authors.lastname: Wild
mesh_terms: D000818:Animals; D001386:Azides / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity*; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000187:drug effects; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics; D009152:Mutagenicity Tests; D009153:Mutagens / Q000633:toxicity*; D012486:Salmonella typhimurium / Q000187:drug effects; D012854:Sister Chromatid Exchange / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D001386:Azides; D002273:Carcinogens; D009153:Mutagens; D004247:DNA; D007041:Hypoxanthine Phosphoribosyltransferase