Photosensitized formation of 8-hydroxy-2'-deoxyguanosine and DNA strand breakage by a cationic meso-substituted porphyrin.
Cationic porphyrins, known to have a high affinity for DNA, are useful tools with which to probe a variety of interactions with DNA. In this study we have examined both DNA strand scission and oxidative DNA base damage, measured by 8-hydroxy-2'-deoxyguanosine (8-OHdG) formation, using a photoactivated cis-dicationic porphyrin. The data demonstrated a dose-dependent formation for each type of DNA damage. Inhibition of strand scission and 8-OHdG formation with the singlet oxygen scavenger 1,3-diphenylisobenzofuran and with MgCl2 and no apparent effect by D2O suggests that a singlet oxygen mechanism generated in close proximity to the DNA may be responsible for the damage. However, a nearly complete inhibition of 8-hydroxy-2'-deoxyguanosine formation in 75% D2O and the substantial enhancement of 8-hydroxy-2'-deoxyguanosine formation in a helium atmosphere by photoactivated porphyrin rules out singlet oxygen as a primary mechanism for this process. These data indicate that distinct mechanisms lead to 8-OHdG formation and strand scission activity.
Nicotera
T M
TM
Roswell Park Cancer Institute, Department of Biophysics, Buffalo, NY 14263-0001.
Munson
B R
BR
Fiel
R J
RJ
D000080242:8-Hydroxy-2'-Deoxyguanosine; D004249:DNA Damage; D004278:DNA, Superhelical / Q000187:drug effects* / Q000302:isolation & purification / Q000528:radiation effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives*; D004587:Electrophoresis, Agar Gel; D004926:Escherichia coli / Q000187:drug effects; D008027:Light; D010782:Photolysis; D017319:Photosensitizing Agents / Q000494:pharmacology*; D010957:Plasmids / Q000187:drug effects* / Q000528:radiation effects; D011166:Porphyrins / Q000494:pharmacology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D018741:Replication Origin / Q000187:drug effects* / Q000528:radiation effects
D004278:DNA, Superhelical; D017319:Photosensitizing Agents; D011166:Porphyrins; D011726:Pyridinium Compounds; C090734:bis(N-methyl-4-dipyridiniumyl)diphenylporphyrin; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine