The photocarcinogenesis of antibiotic lomefloxacin and UVA radiation is enhanced in xeroderma pigmentosum group A gene-deficient mice.
Lomefloxacin (LFLX) is phototoxic and phototumorigenic, but the mechanisms of phototumorigenesis of quinolone drugs have not been fully elucidated. Formation of cyclobutane pyrimidine dimers (CPD) by UVB radiation is primarily involved in the carcinogenesis of ultraviolet (UV) radiation. On the other hand, UVA region is responsible to photobiologic reactions of quinolone drugs. To know if CPD can be formed by UVA radiation in the presence of LFLX and is involved in the phototumorigenesis, we used xeroderma pigmentosum (XP) group A gene-deficient (XPA-/-) mouse, which is defective in nucleotide excision repair. XPA-/- and XPA+/+ mice were irradiated to 5 J per cm2-UVA with or without the administration of LFLX. In XPA-/- mice treated with LFLX, the first skin tumor appeared after exposures to 75 J per cm2 in 5 wk. In XPA+/+ mice treated with LFLX, the first tumor appeared after exposures to 345 J per cm2 in 23 wk. Immunohistochemically, CPD formation was observed after UVA-exposure in the skin of XPA+/+ as well as XPA-/- mice which had been given LFLX. The CPD disappeared, however, earlier from XPA+/+ mice than from XPA-/- mice. The acute inflammatory reaction after LFLX administration and exposure to UVA were greatly enhanced in XPA-/- mice. These results indicate that UVA exposure induces DNA damage in the form of CPD in the presence of LFLX, which exerts phototoxicity and phototumorigenesis.
Itoh
Taketo
T
Department of Dermatology, Kansai Medical University, Moriguchi, Osaka, Japan.
Miyauchi-Hashimoto
Hiroko
H
Sugihara
Akira
A
Tanaka
Kiyoji
K
Horio
Takeshi
T
D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D002273:Carcinogens / Q000633:toxicity; D004249:DNA Damage / Q000235:genetics; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics*; D024841:Fluoroquinolones / Q000633:toxicity*; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000209:etiology* / Q000235:genetics; D017319:Photosensitizing Agents / Q000633:toxicity*; D011740:Pyrimidine Dimers / Q000235:genetics; D015363:Quinolones / Q000633:toxicity*; D012878:Skin Neoplasms / Q000209:etiology* / Q000235:genetics; D014466:Ultraviolet Rays; D051760:Xeroderma Pigmentosum Group A Protein
D000900:Anti-Bacterial Agents; D002273:Carcinogens; D004268:DNA-Binding Proteins; D024841:Fluoroquinolones; D017319:Photosensitizing Agents; D011740:Pyrimidine Dimers; D015363:Quinolones; D051760:Xeroderma Pigmentosum Group A Protein; C497315:Xpa protein, mouse; C053091:lomefloxacin