Human liver slices: An in vitro system for determination of N-acetylation and acetylator status
AuthorGunawardhana, Lhanoo, 1959-
AdvisorSipes, I. Glenn
MetadataShow full item record
PublisherThe University of Arizona.
RightsCopyright © is held by the author. Digital access to this material is made possible by the University Libraries, University of Arizona. Further transmission, reproduction or presentation (such as public display or performance) of protected items is prohibited except with permission of the author.
AbstractAn in vitro system has been developed to study N-acetyltransferase (NAT) activity using human liver slices in dynamic organ culture. Acetylation of para-aminobenzoic acid (PABA) and sulfamethazine (SMZ) in the presence of human liver slices was monitored by measuring the disappearance of the parent amine from the incubation medium using the colorimetric procedure of Bratton & Marshall. Presence of the acetyl conjugate was confirmed using HPLC. PABA acetylation rates varied from 0.72-2.52 nmoles/hr/mg protein (n = 8). This small variation (4 fold) is consistent with the classification of PABA as a monomorphic substrate. The variation in the rate of SMZ acetylation was greater than 20 fold (0.144-3.68 nmoles/hr/mg protein; n = 9). This larger variation is characteristic of SMZ as a polymorphic substrate. The results obtained indicate that human liver slices in dynamic organ culture can be used for the determination of hepatic NAT activity and acetylator status of individual human livers.
Degree ProgramGraduate College
Pharmacology and Toxicology