Photochemical mutagenicity of phototoxic and photochemically carcinogenic fluoroquinolones in comparison with the photostable moxifloxacin.
Certain fluoroquinolone (FQ) antibiotics that show clinical phototoxicity and experimental photochemical carcinogenicity have been found to interact with ultraviolet-A (UVA) radiation to produce oxidative DNA damage in cultured cells and isolated DNA. To study the biological consequences of oxidative DNA damage in mammalian cells, the photochemical mutagenicity of two photoactive FQs, lomefloxacin and Bay y3118, was studied in V79 cells in comparison with that of the photostable moxifloxacin. Lomefloxacin and Bay y3118 were photochemically mutagenic to V79 cells with UVA irradiation, increasing the mutation frequency by about eightfold (400 microM, 6000 J/m2) and tenfold (50 microM, 1000 J/m2), respectively, whereas no photochemical mutagenicity was observed with moxifloxacin (400 microM, 9000 J/m2). We suggest that the previously reported ability of lomefloxacin and Bay y3118 to photochemically produce oxidative DNA damage, which is known to be mutagenic, may be the basis for the photochemical mutagenicity and the reported photochemical carcinogenicity. The photostable moxifloxacin appears to lack such properties.
Jeffrey
A M
AM
Department of Pathology, New York Medical College, Valhalla, NY 10595, USA.
Shao
L
L
Brendler-Schwaab
S Y
SY
Schlüter
G
G
Williams
G M
GM
D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000528:radiation effects / Q000633:toxicity*; D001372:Aza Compounds; D002273:Carcinogens / Q000737:chemistry / Q000528:radiation effects / Q000633:toxicity*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D006224:Cricetinae; D005347:Fibroblasts; D024841:Fluoroquinolones; D000077266:Moxifloxacin; D009153:Mutagens / Q000737:chemistry / Q000528:radiation effects / Q000633:toxicity*; D010777:Photochemistry; D011804:Quinolines; D013056:Spectrophotometry, Ultraviolet; D014466:Ultraviolet Rays
D000890:Anti-Infective Agents; D001372:Aza Compounds; D002273:Carcinogens; D024841:Fluoroquinolones; D009153:Mutagens; D011804:Quinolines; D000077266:Moxifloxacin