A fluoroquinolone antibiotic with a methoxy group at the 8 position yields reduced generation of 8-oxo-7,8-dihydro-2'-deoxyguanosine after ultraviolet-A irradiation

J. E. Rosen, D. Chen, A. K. Prahalad, Thomas Spratt, G. Schluter, G. M. Williams

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

We have previously reported that two fluoroquinolone antibiotics gave rise to 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) in DNA of cells concurrently exposed to UV-A and that this correlated with clinical phototoxicity. To determine the structural basis for generation of oxidative damage, the ability of two synthetic fluoroquinolone candidate antibiotics, Bayer 12-8039 (12-8039) and Bayer Y3118 (Y3118), to give rise to 8-oxo-dG in cultured liver epithelial cells was compared, 12-8039 contains a methoxy group at the 8 position of the quinolone nucleus, whereas Y3118 contains a chlorine group at the same position. Y3118 produced dose-dependent increases in 8-oxo-dG formation in cultured cells after UVA irradiation, whereas the 8-OCH3-substituted 12-8039 produced no increase. Also, after exposure to 20 J/cm2 UVA, UV spectral scans of both compounds revealed that Y3118 underwent photodegradation whereas 12-8039 was stable. These results demonstrate that the presence of an 8-OCH3 group on the quinolone nucleus is important for the reduction of photogeneration of oxidative DNA damage and photodegradation in the presence of UVA irradiation. From this, we suggest that 12-8039 has little phototoxic potential.

Original languageEnglish (US)
Pages (from-to)381-387
Number of pages7
JournalToxicology and Applied Pharmacology
Volume145
Issue number2
DOIs
StatePublished - Jan 1 1997

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Fluoroquinolones
Photolysis
Quinolones
Photodegradation
Irradiation
Anti-Bacterial Agents
Cells
Phototoxic Dermatitis
DNA
Chlorine
Liver
DNA Damage
Cultured Cells
Epithelial Cells
8-oxo-7-hydrodeoxyguanosine

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Pharmacology

Cite this

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title = "A fluoroquinolone antibiotic with a methoxy group at the 8 position yields reduced generation of 8-oxo-7,8-dihydro-2'-deoxyguanosine after ultraviolet-A irradiation",
abstract = "We have previously reported that two fluoroquinolone antibiotics gave rise to 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxo-dG) in DNA of cells concurrently exposed to UV-A and that this correlated with clinical phototoxicity. To determine the structural basis for generation of oxidative damage, the ability of two synthetic fluoroquinolone candidate antibiotics, Bayer 12-8039 (12-8039) and Bayer Y3118 (Y3118), to give rise to 8-oxo-dG in cultured liver epithelial cells was compared, 12-8039 contains a methoxy group at the 8 position of the quinolone nucleus, whereas Y3118 contains a chlorine group at the same position. Y3118 produced dose-dependent increases in 8-oxo-dG formation in cultured cells after UVA irradiation, whereas the 8-OCH3-substituted 12-8039 produced no increase. Also, after exposure to 20 J/cm2 UVA, UV spectral scans of both compounds revealed that Y3118 underwent photodegradation whereas 12-8039 was stable. These results demonstrate that the presence of an 8-OCH3 group on the quinolone nucleus is important for the reduction of photogeneration of oxidative DNA damage and photodegradation in the presence of UVA irradiation. From this, we suggest that 12-8039 has little phototoxic potential.",
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A fluoroquinolone antibiotic with a methoxy group at the 8 position yields reduced generation of 8-oxo-7,8-dihydro-2'-deoxyguanosine after ultraviolet-A irradiation. / Rosen, J. E.; Chen, D.; Prahalad, A. K.; Spratt, Thomas; Schluter, G.; Williams, G. M.

In: Toxicology and Applied Pharmacology, Vol. 145, No. 2, 01.01.1997, p. 381-387.

Research output: Contribution to journalArticle

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T1 - A fluoroquinolone antibiotic with a methoxy group at the 8 position yields reduced generation of 8-oxo-7,8-dihydro-2'-deoxyguanosine after ultraviolet-A irradiation

AU - Rosen, J. E.

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