The initiation activity of norfloxacin does not result in the induction of hepatocellular tumors in rats.
In order to examine whether the in vivo initiation activity of a new quinolone antimicrobial agent -- norfloxacin (NFLX) -- results in the induction of hepatocellular tumors, F344 male rats were subjected to two-thirds partial hepatectomy and oral administration of 1500 or 750mg/kg BW of NFLX or the vehicle once daily for 3 weeks. From 2 weeks after the completion of NFLX treatment, the rats were given 500ppm phenobarbital (PB) in their drinking water for 51 weeks. After the promotion treatment with PB for 17, 34, or 51 weeks, the rats were euthanized under ether anesthesia, and the NFLX-induced hepatic tumors were examined macroscopically by thoroughly sectioning the liver at 5-mm intervals. The liver slices, one each from all liver lobes, were fixed in 10% neutral buffered formalin for immunohistochemical examination of glutathione S-transferase placental form (GST-P) positive foci. NFLX increased neither the incidence of macroscopic hepatic tumors nor the mean number or area of GST-P positive foci. These results suggest that under the present study conditions, the initiation activity of NFLX does not result in the induction of hepatocellular tumors in rats; thus, the initiation activity of NFLX is extremely weak.
Itoh
Tadashi
T
Laboratory of Veterinary Pathology, Faculty of Agriculture, Tokyo University of Agriculture and Technology, Fuchu, Tokyo, Japan. kakuitou@yahoo.co.jp
Moto
Mitsuyoshi
M
Kuroiwa
Yuichi
Y
Sakai
Hiroki
H
Mitsumori
Kunitoshi
K
D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000633:toxicity*; D006528:Carcinoma, Hepatocellular / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005982:Glutathione Transferase / Q000378:metabolism; D006498:Hepatectomy; D008113:Liver Neoplasms / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D008297:Male; D009643:Norfloxacin / Q000633:toxicity*; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344
D000890:Anti-Infective Agents; D002273:Carcinogens; D005982:Glutathione Transferase; D009643:Norfloxacin; D010634:Phenobarbital