Enzymic deacetylation of carcinogenic arylacetamides by tissue microsomes of the dog and other species.
The relative ability of arylacetamide deacetylase enzyme systems of dog liver to carry out the deacetylation of the carcinogens, 4-acetylaminobiphenyl, 2-acetylaminofluorene, and 2-acetylaminaphthalene, was examined. The arylacetamides were incubated with unfortified dog liver microsomes, and enzyme activity (nmol arylamine/mg protein/hr) was estimated by colorimetric quantitation of the resulting arylamines. The dog liver enzyme system displayed characteristics similar to those described for the rodent liver enzyme system in that enzyme activity was greatest in liver tissue, was localized in the microsomal subcellular fraction, required no cofactors, and was inhibited by heat, sodium fluoride, and thiol reagents. In five replicate assays, the relative rates of deacetylation were about 10, 6, and 1 with 4-acetylaminobiphenyl (84.8 +/- 12.4), 2-acetylaminofluorene (52.5 +/- 5.1), and 2-acetylaminonaphthalene (8.8 +/- 3.3), respectively. As a canine urinary bladder carcinogen, 4-acetylaminobiphenyl is considered more potent than 2-acetylaminofluroene, while 2-acetylaminonaphthalene is devoid of detectable carcinogenic activity, despite the fact that 2-aminoaphthalene is a well-established canine urinary bladder carcinogen. Removal of the acetyl group may be a requirement for urinary bladder carcinogenesis; accordingly, the present studies demonstrate the appearance of a direct relationship between dog liver deacetylase enzyme specificity and urinary bladder susceptibility to these carcinogenic arylacetamides.
D015073:2-Acetylaminofluorene / Q000378:metabolism; D000081:Acetamides / Q000378:metabolism*; D000818:Animals; D002273:Carcinogens / Q000378:metabolism*; D006224:Cricetinae; D003640:Dealkylation; D004285:Dogs; D005260:Female; D006168:Guinea Pigs; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D051379:Mice; D008861:Microsomes / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism; D051381:Rats; D013045:Species Specificity; D013997:Time Factors; D001743:Urinary Bladder / Q000648:ultrastructure
D000081:Acetamides; D002273:Carcinogens; D015073:2-Acetylaminofluorene