Lysosomes are sites of fluoroquinolone photosensitization in human skin fibroblasts: A microspectrofluorometric approach

The fluoroquinolone antibiotics are widely used despite their strong photot oxicity under solar UV irradiation. Although they are known as good photody namic photosensitizers, other factors than production of activated oxygen s pecies mag play a role in the effectiveness of the phototoxic effect. Subce llular localization is one of the important parameters that may determine t his strength. Using microspectrofluorometry, it is shown that norfloxacin, ofloxacin, lomefloxacin, ciproflaxin and BAYy3118 are readily incorporated into lysosomes of HS68 human skin fibroblasts although weak staining of the whole cytoplasm also occurs especially with norfloxacin. Consistent with t heir photoinstability in solutions, the fluoroquinolones under study are re adily photobleached by UVA in the HS68 fibroblasts. The BAYy3118 derivative that has the fastest bleaching rate also shows the strongest phototoxicity toward HS68 fibroblasts. Photosensitization with these fluoroquinolones in duces lysosomal membrane damage as shown by the increased rate of leakage o f the lysosomal probe lucifer yellow as compared to that observed with untr eated cells.