Microsomal deacetylation of isomeric acetamidobiphenyls.
In vitro rates of deacetylation were measured with carcinogenic and noncarcinogenic isomeric arylamides using microsomal preparations from guinea pig, hamster, rat, mouse, rabbit and dog. Following incubation at 37 degrees, the substrate and hydrolysis products were extracted into ether and the corresponding aromatic amine quantified by gas-liquid chromatography. The data show that rates of deacetylation were both species and isomer dependent. In general, the highest rate of deacetylation in microsomes from all species was recorded with 2-acetamidobiphenyl (2-AABP); however, the mouse uniquely deacetylated 4-acetamidobiphenyl (4-AABP) most rapidly. The meta isomer 3-acetamidobiphenyl (3-AABP) was deacetylated at an intermediate rate in all species investigated. The variability in the rates of deacetylation within species may reflect the heterogeneity of the deacetylase enzymes and may be an important factor in amine/amide carcinogenesis.
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Chelsea Department of Pharmacy, King's College, University of London, U.K.
Gorrod
J W
JW
D000611:Aminobiphenyl Compounds / Q000378:metabolism*; D000818:Animals; D006224:Cricetinae; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D007536:Isomerism; D008297:Male; D008647:Mesocricetus; D051379:Mice; D008815:Mice, Inbred Strains; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D010261:Paraoxon / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D012969:Sodium Fluoride / Q000494:pharmacology; D013045:Species Specificity
D000611:Aminobiphenyl Compounds; D012969:Sodium Fluoride; D011335:Proadifen; D010261:Paraoxon