Distinct mechanisms of guanine-specific DNA photodamage induced by nalidixic acid and fluoroquinolone antibacterials.

摘要: Abstract Fluoroquinolone antibacterials, which have been used for the treatment of a variety infectious diseases, are reported to be photocarcinogenic. We investigated mechanisms DNA damage by UVA radiation (365 nm) plus fluoroquinolone antibacterials using 32 P-labeled fragments obtained from human c-Ha- ras -1 proto-oncogene and p53 tumor suppressor gene. Photocarcinogenic nalidixic acid (NA), is an old member synthetic quinolone caused specifically at 5′- G G-3′ sequences, whereas lomefloxacin (LFLX) did not exhibit site preference consecutive guanines. LFLX-induced photodamage was inhibited sodium azide enhanced in D 2 O, suggesting that singlet oxygen plays key role damage. LFLX induced formation 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) depending on concentrations, 8-oxodG single-stranded DNA. In contrast, NA larger amounts double-stranded ESR spin destruction method revealed through electron transfer but not. These findings indicate photoactivated important expression their photocarcinogenicity.