Mutagenicity of o-anisidine to the bladder of lacI- transgenic B6C3F1 mice: absence of 14C or 32P bladder DNA adduction.
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.
Ashby
J
J
Zeneca Central Toxicology Laboratory, Alderley Park, Cheshire, UK.
Short
J M
JM
Jones
N J
NJ
Lefevre
P A
PA
Provost
G S
GS
Rogers
B J
BJ
Martin
E A
EA
Parry
J M
JM
Burnette
K
K
Glickman
B W
BW
D000814:Aniline Compounds / Q000378:metabolism* / Q000633:toxicity*; D000818:Animals; D002250:Carbon Radioisotopes; D002273:Carcinogens / Q000378:metabolism* / Q000633:toxicity*; D004247:DNA / Q000187:drug effects* / Q000378:metabolism*; D018736:DNA Adducts / Q000096:biosynthesis / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009152:Mutagenicity Tests; D009154:Mutation; D010761:Phosphorus Radioisotopes; D001743:Urinary Bladder / Q000187:drug effects* / Q000378:metabolism*
D000814:Aniline Compounds; D002250:Carbon Radioisotopes; D002273:Carcinogens; D018736:DNA Adducts; D010761:Phosphorus Radioisotopes; D004247:DNA; C003898:2-anisidine