In vivo photochemical micronucleus induction due to certain quinolone antimicrobial agents in the skin of hairless mice.
The skin micronucleus test combined with irradiation due to a sunlight simulator having a spectrum almost identical to solar irradiation was used as a novel in vivo testing method for detecting or comparing the photochemical chromosome damage of quinolone antibacterial agents (quinolones). Eight-week-old male SKH1 hairless mice were orally administered once lomefloxacin (LFLX), a strong in vitro photochemical clastogen, at 25 or 50 mg/kg, followed by light irradiation at 7.9-9.4J/cm2 of ultraviolet A (UVA). Animals were killed on Days 2, 3, 4, 5 or 8 (the dosing day was designated as Day 1), and the incidence of micronucleus in the epidermis was determined. As results, LFLX at either dose caused significant increases in the micronucleus frequency, which peaked on Day 4. These changes tended to return to the control level on Day 8. Then, the micronucleus induction potential of the quinolone derivatives levofloxacin (LVFX) and clinafloxacin (CLFX) at 10, 20 or 40 mg/kg was assessed on Day 4 under the same experimental conditions as for LFLX. Although LVFX was negative even at 40 mg/kg, CFLX dose-dependently induced significant increases in micronucleus frequency at all doses. The correlation of magnitude among the three quinolones in the skin micronucleus test with light irradiation was similar to that in our previous in vitro photochemical clastogenicity study. No significant increase in micronucleus frequency was observed in any of three quinolones employed without light irradiation. In conclusion, the experimental method presented here would be a useful tool for detecting in vivo photochemical chromosome damage and for research on photochemical carcinogenesis of chemicals.
Itoh
Satoru
S
Drug Safety Research Laboratory, Daiichi Pharmaceutical Co. Ltd., 16-13, Kita-Kasai 1-Chome, Edogawa-ku, 134-8630, Tokyo, Japan. itohsudk@daiichipharm.co.jp
Katoh
Michiyuki
M
Furuhama
Kazuhisa
K
D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology*; D002869:Chromosome Aberrations / Q000187:drug effects* / Q000528:radiation effects*; D004305:Dose-Response Relationship, Drug; D024841:Fluoroquinolones; D064704:Levofloxacin; D008027:Light; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D048629:Micronuclei, Chromosome-Defective / Q000187:drug effects / Q000528:radiation effects; D015162:Micronucleus Tests; D015242:Ofloxacin / Q000494:pharmacology; D017319:Photosensitizing Agents / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects* / Q000528:radiation effects; D013997:Time Factors
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D017319:Photosensitizing Agents; D015363:Quinolones; D064704:Levofloxacin; C057477:clinafloxacin; D015242:Ofloxacin; C053091:lomefloxacin