Effect of the new quinolone antibacterial agent levofloxacin on multiple organ carcinogenesis initiated with wide-spectrum carcinogens in rats.
A multiple organ carcinogenesis model was used in male F344 rats to test the carcinogenic potential of (-)-(S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo- 7H-pyrido[1,2,3-de][1,4] benzoxazine-6-carboxylic acid hemihydrate (levofloxacin, DR-3355, CAS 10086-85-4). After sequential treatment with diethylnitrosamine (DEN: carcinogen for the liver), N-methylnitrosourea (MNU: carcinogen for the esophagus, forestomach and thyroid) and dihydroxy-di-N-propylnitrosamine (DHPN: carcinogen for the lungs, kidney and urinary bladder), rats were treated with DR-3355, N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN), N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), catechol (CC) or phenobarbital (PB) to examine whether these compounds modified the carcinogenesis in multiple organs. As a result of histopathological examinations at study week 20, DR-3355 did not induce neoplastic lesions, nor did it enhance the occurrences of proliferative preneoplastic lesions. In contrast, BBN increased the incidences of hyperplasias and papillomas of the urinary bladder. CC enhanced the occurrences of hyperplasias and papillomas of the forestomach as well as submucosal glandular growth for the glandular stomach. PB increased the number of altered cell foci in the liver and the incidence of follicular cysts and hyperplasias of the thyroid. These results indicate that DR-3355 is not capable of promoting the development of tumors in rat multiple organs.
Kajimura
T
T
Drug Safety Research Center, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Tojo
H
H
Kudo
G
G
Yamada
M
M
Domon
S
S
Nomura
M
M
Takayama
S
S
D000818:Animals; D000890:Anti-Infective Agents / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens / Q000633:toxicity*; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D064704:Levofloxacin; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D015242:Ofloxacin / Q000633:toxicity*; D051381:Rats; D011916:Rats, Inbred F344
D000890:Anti-Infective Agents; D002273:Carcinogens; D064704:Levofloxacin; D015242:Ofloxacin