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| Content Provider | PubMed Central |
|---|---|
| Author | Blum, M. Grant, D. M. Demierre, A. Meyer, U. A. |
| Abstract | The New Zealand White rabbit provides a widely used animal model for the human acetylation polymorphism, which confers marked interindividual variation in the effect and toxicity of numerous drugs, chemicals, and potential carcinogens. The relationship of a recently isolated cDNA clone, designated rnat, to genetically polymorphic arylamine N-acetyltransferase (NAT; acetyl-CoA:arylamine N-acetyltransferase, EC 2.3.1.5) of rabbit liver was established by its expression in monkey kidney COS-1 cells: (i) cytosols from transfected cultures contained high levels of an Ac-CoA-dependent NAT activity, which was kinetically indistinguishable from that observed in cytosols from livers of genetically rapid-acetylator rabbits; (ii) transfected cells also contained an immunoreactive protein, recognized by NAT-specific antibodies, with identical electrophoretic mobility to NAT from rabbit liver. The rnat clone and anti-NAT antibodies were then used to study the relationship between NAT activity, liver enzyme protein, and the level of mRNA in livers from in vivo phenotyped rapid- and slow-acetylator rabbits. Livers from slow acetylators were devoid of both immunodetectable NAT protein and its corresponding mRNA. Analysis of genomic DNA with a panel of restriction enzymes revealed the loss of specific hybridizing bands in the DNA of slow-acetylator rabbits. These data strongly suggest that defective arylamine N-acetylation in the rabbit model is caused by a gene deletion resulting in an absence of specific mRNA and NAT enzyme protein. |
| Starting Page | 9554 |
| File Format | |
| ISSN | 10916490 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 23 |
| Volume Number | 86 |
| Language | English |
| Publisher Date | 1989-12-01 |
| Access Restriction | Open |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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