MUTAGENICITY OF O-ANISIDINE TO THE BLADDER OF LACI(-) TRANSGENIC B6C3F1 MICE - ABSENCE OF C-14 OR P-32 BLADDER DNA ADDUCTION

Earlier studies have established that the rodent bladder carcinogen o- anisidine (OA) gives negative results in all of the standard rodent ge netic toxicity assays. In the present study, a single oral administrat ion of the maximum tolerated dose level (750 mg/kg) of OA to B6C3F1 mi ce yielded negative results in P-32-post-labelling assays of bladder a nd liver DNA (24 h after dosing). Likewise, C-14-ring-labelled OA admi nistered orally to B6C3F1 mice gave no evidence of DNA binding 6, 12 o r 24 h later. Administration of OA (750 mg/kg) to transgenic lacI(-) m ice (Big Blue(TM)) led to a small increase in mutation frequency (MF) in the bladder, but not in the liver. Increased MFs were observed in t he bladder following 1, 3 or 10 daily doses with sampling times of 1 o r 2 weeks after the final dose. However, statistical significance (P < 0.01) was only reached 2 weeks after either 3 or 10 daily administrat ions 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 radi cal species is suggested.