Mutagenicity of o-anisidine to the bladder of lacI- transgenic B6C3F1 mice: absence of 14C or 32P bladder DNA adduction.

Abstract

Earlier studies have established that the rodent bladder carcinogen o-anisidine (OA) gives negative results in all of the standard rodent genetic toxicity assays. In the present study, a single oral administration of the maximum tolerated dose level (750 mg/kg) of OA to B6C3F1 mice yielded negative results in 32P-post-labelling assays of bladder and liver DNA (24 h after dosing). Likewise, 14C-ring-labelled OA administered orally to B6C3F1 mice gave no evidence of DNA binding 6, 12 or 24 h later. Administration of OA (750 mg/kg) to transgenic lacI- mice (Big Blue) led to a small increase in mutation frequency (MF) in the bladder, but not in the liver. Increased MFs were observed in the bladder following 1, 3 or 10 daily doses with sampling times of 1 or 2 weeks after the final dose. However, statistical significance (P < 0.01) was only reached 2 weeks after either 3 or 10 daily administrations of OA. The positive control chemical (dimethylnitrosamine) gave a positive result (P < 0.01) in the liver, but not the bladder, 7 days after a single administration of 10 mg/kg. The possibility that OA is mutagenic and carcinogenic to the rodent bladder via formation of radical species is suggested.