Photochemical mutagenicity of phototoxic and photochemically carcinogenic fluoroquinolones in comparison with the photostable moxifloxacin

Citation
Am. Jeffrey et al., Photochemical mutagenicity of phototoxic and photochemically carcinogenic fluoroquinolones in comparison with the photostable moxifloxacin, ARCH TOXIC, 74(9), 2000, pp. 555-559
Citations number
25
Categorie Soggetti
Pharmacology & Toxicology
Journal title
ARCHIVES OF TOXICOLOGY
ISSN journal
03405761 → ACNP
Volume
74
Issue
9
Year of publication
2000
Pages
555 - 559
Database
ISI
SICI code
0340-5761(200011)74:9<555:PMOPAP>2.0.ZU;2-4
Abstract
Certain fluoroquinolone (FQ) antibiotics that show clinical phototoxicity a nd experimental photochemical carcinogenicity have been found to interact w ith ultraviolet-ii (UVA) radiation to produce oxidative DNA damage in cultu red cells and isolated DNA. To study the biological consequences of oxidati ve DNA damage in mammalian cells, the photochemical mutagenicity of two pho toactive FQs, lomefloxacin and Bay y3118, was studied in V79 cells in compa rison with that of the photostable moxifloxacin. Lomefloxacin and Bay y3118 were photochemically mutagenic to V79 cells with UVA irradiation, increasi ng the mutation frequency by about eightfold (400 muM, 6000 J/m(2)) and ten fold (50 muM, 1000 J/m(2)), respectively, whereas no photochemical mutageni city was observed with moxifloxacin (400 muM, 9000 J/m(2)). We suggest that the previously reported ability of lomefloxacin and Bay y3118 to photochem ically produce oxidative DNA damage, which is known to be mutagenic, may be the basis for the photochemical mutagenicity and the reported photochemica l carcinogenicity. The photostable moxifloxacin appears to lack such proper ties.