Radiation-activated nuclease activity of o,o'-Diphenyleneiodonium cations (DPI): a reductively initiated chain reaction involving the C1' chemistry.
o,o'-Diphenyleneiodonium cations (DPI) convert relatively harmless radiation-produced electrons into efficient DNA cleaving agents. The cleavage products are unaltered DNA bases, 5-methylenefuranone (5-MF), and a complete set of 3' and 5'-phosphorylated DNA fragments. The production of alkali-labile sites is a minor factor in the process. Based on the production of 5-MF, it is concluded that DNA cleavage by DPI cations involves (but may not be limited to) the C1' chemistry. The loss of 3-aminoDPI (ADPI) cations bound to highly polymerized calf thymus DNA appears to be due to a short-chain reaction with an apparent length of up to 2.1 ADPI cations consumed for each radiation-produced electron. The suggested chain reaction mechanism includes the one-electron oxidation of DNA radicals (including the C1' sugar radical) by ADPI cations bound to the same duplex. The yields of DNA loss in complexes formed by ADPI with short synthetic duplexes indicate that there is more than a 60% probability of DNA damage after one-electron reduction of ADPI.
Razskazovskiy
Yuriy
Y
Department of Physics and Astronomy, Box 70652, East Tennessee State University, Johnson City, Tennessee 37614, USA. raiskazy@etsu.edu
D000818:Animals; D002412:Cations; D002417:Cattle; D003037:Cobalt Radioisotopes; D004247:DNA / Q000378:metabolism / Q000528:radiation effects*; D004249:DNA Damage; D004583:Electrons; D004791:Enzyme Inhibitors / Q000378:metabolism / Q000528:radiation effects*; D005663:Furans / Q000032:analysis; D005720:Gamma Rays; D007700:Kinetics; D008956:Models, Chemical; D009861:Onium Compounds / Q000378:metabolism / Q000528:radiation effects*; D010880:Piperidines / Q000494:pharmacology
C473701:3-aminodiphenyleneiodium; D002412:Cations; D003037:Cobalt Radioisotopes; D004791:Enzyme Inhibitors; D005663:Furans; D009861:Onium Compounds; D010880:Piperidines; C037354:protoanemonin; C032727:piperidine; C007517:diphenyleneiodonium; D004247:DNA