Comutagenesis-IV in vitro metabolism of the comutagen 2-amino-3-methylpyridine: species differences and metabolic interaction with norharman.
The metabolism of 2-amino-3-methylpyridine (2A3MP) in vitro has been investigated using the rat, rabbit, dog, marmoset, guinea pig and hamster hepatic microsomes and S9 supernatants (10,000 g fraction). Species differences were observed in the in vitro formation of 2-amino-3-methylpyridine-N-oxide (2A3MPNO), 2-amino-3-hydroxymethylpyridine (2A3HMP) and 2-amino-3-methyl-5-hydroxypyridine (2A3M5HP). The order of activity for 2A3MPNO using hepatic microsomes was dog > rat > rabbit > guinea pig > marmoset > hamster, for 2A3HMP dog > hamster > guinea pig > rat > rabbit > marmoset, for 2A3M5HP rabbit > hamster > dog > rat > guinea pig > marmoset. When hepatic S9 supernatants from various uninduced species were used, rabbit was more active for the production of 2A3MPNO and 2A3M5HP whilst hamster was more effective for the formation of 2A3HMP. Pretreatment of rats with arochlor 1254 enhanced the formation of all metabolites. No species produced a metabolite having the properties of 2-hydroxylamino-3-methylpyridine or further oxidation or condensation products. The present study did not show the presence of any new metabolite after co-incubation of 2A3MP with norharman.
Altuntas
T G
TG
Chelsea Department of Pharmacy, King's College London, University of London, U.K.
Gorrod
J W
JW
D000631:Aminopyridines / Q000493:pharmacokinetics*; D000818:Animals; D001140:Aroclors / Q000494:pharmacology; D001711:Biotransformation; D002144:Callithrix; D002243:Carbolines; D002273:Carcinogens / Q000494:pharmacology; D020111:Chlorodiphenyl (54% Chlorine); D006224:Cricetinae; D003600:Cytosol / Q000378:metabolism; D004285:Dogs; D006168:Guinea Pigs; D006247:Harmine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D006900:Hydroxylation; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009153:Mutagens / Q000493:pharmacokinetics*; D010084:Oxidation-Reduction; D010847:Picolines / Q000493:pharmacokinetics*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar; D013045:Species Specificity
D000631:Aminopyridines; D001140:Aroclors; D002243:Carbolines; D002273:Carcinogens; D009153:Mutagens; D010847:Picolines; D020111:Chlorodiphenyl (54% Chlorine); D006247:Harmine; C010262:norharman; C109727:2-amino-3-methylpyridine