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Hiraku Y, Kawanishi S: Distinct mechanisms of guanine-specific DNA photodamage induced by nalidixic acid and fluoroquinolone antibacterials. Arch Biochem Biophys. 2000 Oct 15;382(2):211-8.
Fluoroquinolone antibacterials, which have been used for the treatment of a variety of infectious diseases, are reported to be photocarcinogenic. We investigated the mechanisms of DNA damage by UVA radiation (365 nm) plus fluoroquinolone antibacterials using 32P-labeled DNA fragments obtained from the human c-Ha-ras-1 proto-oncogene and the p53 tumor suppressor gene. Photocarcinogenic nalidixic acid (NA), which is an old member of synthetic quinolone antibacterials, caused DNA damage specifically at 5'-GG-3' sequences, whereas lomefloxacin (LFLX) did not exhibit the site preference for consecutive guanines. LFLX-induced DNA photodamage was inhibited by sodium azide and enhanced in D2O, suggesting that singlet oxygen plays the key role in the DNA damage. LFLX plus UVA induced the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) depending on LFLX concentrations, and 8-oxodG formation was enhanced in single-stranded DNA. In contrast, NA induced larger amounts of 8-oxodG in double-stranded DNA. ESR spin destruction method revealed that NA induced DNA photodamage through electron transfer but LFLX did not. These findings indicate that DNA damage induced by photoactivated LFLX and NA plays an important role in expression of their photocarcinogenicity. |
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