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.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
