The experimental results on chromosomal aberrations and spindle disturbances in mammalian liver cells for eight regioisomers of pyrene, benzo(a)pyrene and phenanthrene quinones were compared with the AM1 calculated stereoelectronic descriptors. The electronic structure of the parent compounds as well as the corresponding radical anions, were evaluated. Two groups of reactivity descriptors were specified evaluating the mechanisms of genotoxicity of quinones that were recently proposed by us. The first group of parameters (e.g., electronic gap) describes potency of chemicals as cross-linkers of cellular macromolecules, whereas the second group (e.g., electronegativity, frontier orbital energies, their displacement and energy equivalence when going from quinones to the respective intermediate anion-radicals) assesses the one electron reduction efficiency. The ordering of quinones, according to their theoretically estimated reactivities, was found to be consistent with the experimental genotoxicity data. It was concluded that genotoxic activity of studied quinones is an integrated effect of two mechanisms. The prevailing one of these mechanisms affects the qualitative difference in the genotoxic effect of quinones. The benzo(a)pyrene and pyrene quinones were predicted to be more active cross-link inducers and more effective oxidants than phenanthrene quinones.
Qsar for clastogenic effects induced by regioisomers of PAH quinones
SBRANA, ISABELLA;
1996-01-01
Abstract
The experimental results on chromosomal aberrations and spindle disturbances in mammalian liver cells for eight regioisomers of pyrene, benzo(a)pyrene and phenanthrene quinones were compared with the AM1 calculated stereoelectronic descriptors. The electronic structure of the parent compounds as well as the corresponding radical anions, were evaluated. Two groups of reactivity descriptors were specified evaluating the mechanisms of genotoxicity of quinones that were recently proposed by us. The first group of parameters (e.g., electronic gap) describes potency of chemicals as cross-linkers of cellular macromolecules, whereas the second group (e.g., electronegativity, frontier orbital energies, their displacement and energy equivalence when going from quinones to the respective intermediate anion-radicals) assesses the one electron reduction efficiency. The ordering of quinones, according to their theoretically estimated reactivities, was found to be consistent with the experimental genotoxicity data. It was concluded that genotoxic activity of studied quinones is an integrated effect of two mechanisms. The prevailing one of these mechanisms affects the qualitative difference in the genotoxic effect of quinones. The benzo(a)pyrene and pyrene quinones were predicted to be more active cross-link inducers and more effective oxidants than phenanthrene quinones.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
