Molecular mechanism of drug photosensitization. IX. Effect of inorganic ions on DNA cleavage photosensitized by naproxen.
Photocleavage of DNA induced by naproxen and the correlated protective effect by some inorganic ions have been considered. The presence of a DNA complex is suggested and only associated naproxen seems to be responsible for the cleavage, for which the quantum yield of single strand breaks was calculated. The inorganic ions I-, Mn2+, Co2+ and Cu2+ decrease naproxen-photoinduced DNA cleavage. Iodide acts by a heavy atom mechanism, thus inhibiting naproxen photolysis and decreasing the amount of free radicals responsible for the photocleavage both in aerobic and anaerobic conditions. Metallic ions protect only within a range of concentrations, as for higher amounts damaging processes are observed. The protective efficiency of cations decreases with the increase of free drug concentration in the bulk of the solution, due to their involvement in the scavenging of naproxen radicals generated by photolysis of the free drug. In the presence of EDTA the cations show a better protective action. The most likely hypothesis is an inhibiting effect on the damaging processes via a redox cycle. The different behaviors of copper and of the two other cations can be justified by the influence of redox potentials of free and complexed metals and by the superoxide dismutase-like activity of copper.
De Guidi
G
G
Dipartimento di Scienze Chimiche, Università di Catania, Italy.
Giuffrida
S
S
Condorelli
G
G
Costanzo
L L
LL
Miano
P
P
Sortino
S
S
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D002412:Cations; D002417:Cattle; D004247:DNA / Q000737:chemistry / Q000187:drug effects* / Q000528:radiation effects*; D004249:DNA Damage; D066298:In Vitro Techniques; D009288:Naproxen / Q000494:pharmacology*; D010777:Photochemistry
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002412:Cations; D009288:Naproxen; D004247:DNA