Expression and regulation of cytochrome P-450I genes (CYP1A1 and CYP1A2) in the rat alimentary tract
| Autor: | Wei Wang, Peter G. Traber, Roxanne Florence, W. Michael McDonnell |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
Male
Transcription Genetic Molecular Sequence Data Biophysics Gene Expression Aromatic hydrocarbon receptor Biology Polymerase Chain Reaction Biochemistry Gene Expression Regulation Enzymologic Esophagus Cytochrome P-450 Enzyme System beta-Naphthoflavone Reference Values Structural Biology Gene expression Genetics medicine Animals RNA Messenger Northern blot Intestinal Mucosa Benzoflavones Cell Nucleus Gastrointestinal tract Messenger RNA Mucous Membrane Base Sequence CYP1A2 Cytochrome P450 Blotting Northern Molecular biology Rats Inbred F344 Small intestine Rats medicine.anatomical_structure Liver Oligodeoxyribonucleotides Gastric Mucosa Enzyme Induction Phenobarbital biology.protein DNA Probes Methylcholanthrene |
| Zdroj: | Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 1171:167-175 |
| ISSN: | 0167-4781 |
| Popis: | Cytochrome P-450 (P450) enzymes in the mucosa of the alimentary tract may be involved in the activation and/or inactivation of ingested xenobiotics and procarcinogens. Since the multiple P450 enzymes have overlapping substrate specificities and, in some cases, similar antigenic determinants, definitive identification of P450 genes that are expressed in various tissues requires molecular analysis. In this study, a sensitive and specific polymerase chain reaction assay along with hybridization analysis was used to examine the expression of the CYP1A gene family in the rat alimentary tract. CYP1A1 mRNA was expressed throughout the alimentary tract in untreated rats, as determined by the polymerase chain reaction. However, Northern blot analysis detected CYP1A1 mRNA and enzymatic activity only in small intestine and liver, with greater amounts in intestine. After treatment with beta-naphthoflavone, CYP1A1 mRNA and enzymatic activity was markedly induced in each alimentary tissue including esophagus, fore-stomach, glandular stomach, small intestine and colon. A single dose of inducer resulted in a rapid rise in CYP1A1 mRNA which was shown by nuclear run-on assays to be primarily due to an increase in transcription of the CYP1A1 gene. CYP1A2 mRNA was detected in significant amounts only in glandular stomach following induction although the polymerase chain reaction assay identified low levels of CYP1A2 mRNA in several other tissues. The definitive identification of the CYP1A genes that are expressed in alimentary tissue will allow the design of experiments to investigate the importance of these enzymes in the metabolism of carcinogens, and ultimately carcinogenesis, in the gastrointestinal tract. In addition, these data suggest that the aromatic hydrocarbon receptor, which mediates transcriptional induction of multiple genes by xenobiotics, is expressed through the alimentary tract. |
| Databáze: | OpenAIRE |
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