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Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
Published on: March 20, 2018
Comparison between photo-induction and microsomal activation of polycyclic hydrocarbons with different oncogenic
G Prodi1, S Grilli, M Mazzullo
1Centro di Cancerogenesi Chimica, Istituto di Cancerologia, Università degli Studi di Bologna, Italy.
Abstract:
The binding of five polycyclic aromatic hydrocarbons (PAH) (anthracene (A), benzo(a)anthracene (BA), dibenz(a,h)anthracene (DBA), benzo(a)pyrene (BP) and 7,12-dimethylbenz(a)anthracene (DMBA)) to calf thymus DNA and synthetic polyribonucleotides was studied. Binding was mediated by near-ultraviolet (NUV) irradiation and 3-methylcholanthrene-induced microsomes from rat liver, in order to compare the effectiveness of these two activating systems in forming in vitro intermediates capable of binding covalently to nucleic acids. With NUV irradiation, an interaction among PAH and nucleic acids was obtained regardless of the PAH or the nucleic acid employed. The effectiveness of this activating system was higher (between 1 to 2 orders of magnitude) than that shown by induced microsomes. The enzymatic pathway bioactivated all PAH, except A, to interact with DNA. Therefore, a certain degree of correlation between the extent of DNA binding and oncogenic potency of the chemicals seemed to exist. Polynucleotide labeling was always higher than DNA labeling.
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