Mutagenicity of urine from rats after administration of 2,4-diaminoanisole: the effect of microsomal enzyme inducers.
Ring 14C-labelled 2,4-diaminoanisole disulfate was administered to rats pretreated with the microsomal inducers phenobarbital (PB), beta-naphthoflavone (BNF), 3-methylcholanthrene (MC) or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). The 24-h urine from rats pretreated with PB showed a 2-fold increase in revertant rate over the corresponding control as measured by the Ames Salmonella test system. Pretreatment of rats with BNF, MC or TCDD decreased the mutagenicity of urine by about 70% when an activating system was used. However, in the absence of an activating system, the urine from rats induced with BNF, MC or TCDD showed a significant (P < 0.001) degree of mutagenicity compared with urine from controls or urine from phenobarbital-induced rats. Release of conjugates by beta-glucuronidase increased the mutagenicity of urine even in the absence of an activating system, but the number of revertants was almost doubled in the presence of an activating system. The urine from rats treated only with the 4 inducers did not show any mutagenicity. 2,4-Diaminoanisole itself was mutagenic only in the presence of an activating system. alpha-Naphthoflavone (ANF) (0.1 mM) inhibited by 85--90% the in vitro mutagenicity of urine, mediated by Aroclor 1254, MC or TCDD induced rat-liver microsomes. The mutagenicity mediated through PB-induced rat-liver microsomes was, however, inhibited only by 16%. Similarly, 0.1 mM metyrapone (MP) inhibited the mutagenicity of urine by Aroclor 1254, MC or TCDD induced rat-liver microsomes by 13--18%. For the same MP concentration a 50% inhibition of the mutagenicity mediated through PB-induced rat-liver microsomes was observed. The mutagenicity pattern for urine in vitro was shown to be similar with liver S9 from rats induced either with Aroclor 1254 or with MC.
D000818:Animals; D000840:Anisoles / Q000494:pharmacology / Q000652:urine; D001571:Benzoflavones / Q000494:pharmacology; D001711:Biotransformation / Q000187:drug effects; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D009152:Mutagenicity Tests; D009153:Mutagens; D010424:Pentobarbital / Q000494:pharmacology; D010655:Phenylenediamines / Q000494:pharmacology* / Q000652:urine; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D051381:Rats; D012486:Salmonella typhimurium / Q000235:genetics; D019324:beta-Naphthoflavone
D000840:Anisoles; D001571:Benzoflavones; D009153:Mutagens; D010655:Phenylenediamines; D000072317:Polychlorinated Dibenzodioxins; D008748:Methylcholanthrene; D019324:beta-Naphthoflavone; C007294:4-methoxy-3-phenylenediamine; D010424:Pentobarbital