COMUTAGENESIS .3. IN-VITRO METABOLISM OF 2-AMINO-3-METHYLPYRIDINE - THE EFFECT OF VARIOUS POTENTIAL INHIBITORS, ACTIVATORS AND INDUCERS

1. The effects of various potential inhibitors, activators and inducer s on the metabolism of the comutagen 2-amino-3-methylpyridine (2A3MP) by rabbit hepatic microsomes and S9 supernatants have been studied. 2. The 1-N-oxidation of 2A3MP to 2-amino-3-methylpyridine-1-N-oxide (2A3 MPNO) was inhibited by 2,4-dichloro-6-phenykphenoxyeethylamine (DPEA), 2-diethylaminoethyl-2,2-diphenylvalerate (SKF 525-A) and n-octylamine . 3. The C-oxidation products of 2A3MP, i.e. 2-amino-3-hydroxymethylpy ridine (2A3HMP) and 2-amino-3-methyl-5-hydroxypyridine (2A3M5HP), were also inhibited by these compounds. 4. Pretreatment of animals with ph enobarbitone (PB) resulted in an increase in the production of 2A3MPNO and 2A3HMP, whereas beta-naphthoflavone (BNF) pretreatment had a grea ter effect on the formation of 2A3M5HP. 5. Pretreatment with pyridine or pyrazine also had an appreciable effect on the formation of 2A3HMP. 6. It is suggested that different cytochrome P450 isozymes are respon sible for the metabolic profile of 2A3MP. CYP2B was involved in the N- oxidation; 2E and/or 2B in the formation of 2A3HMP, and 3A and/or 1A i n the formation of 2A3M5HP.