Abstract
The promoting effect of nalidixic acid (NA), an old quinolone antibacterial agent, was investigated in a two-stage preputial/clitoral gland carcinogenesis model in F344 rats initiated with 3, 2'-dimethyl-4-aminobiphenyl (DMAB). 3, 3'-Dimethoxybenzidine dihydrochloride (DMOB) was used as a genotoxic carcino-gen for the preputial/clitoral gland. After that, ofloxacin (OFLX), a new quinolone antibacterial agent, was examined. Male and female rats were given weekly subcutaneous injections of DMAB at a dose of 50mg/kg body weight, for a total of 8 times. Ten weeks after the commencement of DMAB treatment, rats were given 4, 000ppm NA in the diet, 330ppm DMOB in the drinking water or 4, 000ppm OFLX in thediet for the next 26 or 42 weeks. Upon histopathological investigation at experimental weeks 36 and 52, preputial/clitoral gland adenomas and carcinomas, respectively, were found in rats given DMAB alone. NA or DMOB administration after DMAB treatment enhanced the incidences of adenomas or carcinomas of the preputial/clitoral gland whereas OFLX did not. Meanwhile, NA is known to be a non-genotoxicagent. The present results indicate that NA is a tumor promoter in the preputial/clitoral gland of rats.
