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CYTOCHROME P450 GENE EXPRESSION IN THE SPRAGUE-DAWLEY RAT (3-METHYLCHOLANTHRENE, PHENOBARBITAL, NUCLEAR RNA)
Abstract
This dissertation attempted to investigate the mechanisms underlying cytochrome P-450 gene expression in the Sprague-Dawley rat. Various cDNA and genomic DNA clones containing information for cytochromes P-450c/d and a cytochrome P-450b/e-like protein were employed as probes to study the structure and/or expression of these genes in various tissues. Northern blot analysis revealed multiple nuclear RNAs homologous to each of these probes. The cytochrome P-450d and P-450b/e-like nuclear mRNAs were constitutively expressed in rat liver unlike the cytochrome P-450c nuclear mRNA. The cytochrome P-450c/d nuclear RNAs were inducible by 3-methylcholanthrene, isosafrole and Araclor 1254. The cytochrome P-450b/e-like nuclear RNAs were inducible by phenobarbital, 3-methylcholanthrene and Araclor 1254. The primary nuclear RNA transcript from the cytochrome P-450c gene was identified. A "superinduction" of cytochrome P-450c gene expression was observed in liver during the partial inhibition of protein synthesis in vivo. Cytochrome P-450c nuclear RNA was also inducible in fetal liver and adult lung, kidney and spleen. Cytochrome P-450c/d nuclear RNA was constitutively expressed in testes, and was not detected in brain. No cytochrome P-450d nuclear RNA was detected in lung and spleen. No differences were detected in a 9.2 kbp chromosomal domain encompassing the cytochrome P-450c gene in adult and fetal liver, and adult kidney, lung, spleen, and testes. A DNAase I-hypersensitive region at -3.2 to -5.1 kbp was observed in fetal and adult liver. Induction of cytochrome P-450c gene expression in adult liver resulted in a general increase in DNAase I-sensitivity that was most notable in the 5' regions, and that approached the sensitivity of the albumin gene in this tissue. The structural regions of the cytochrome P-450c gene were generally more resistant to DNAase I digestion than the albumin gene in control and "induced" fetal liver, and in control adult kidney and lung.
Subject Area
Molecular biology
Recommended Citation
FOLDES, ROBERT LESLIE, "CYTOCHROME P450 GENE EXPRESSION IN THE SPRAGUE-DAWLEY RAT (3-METHYLCHOLANTHRENE, PHENOBARBITAL, NUCLEAR RNA)" (1986). ETD collection for University of Nebraska-Lincoln. AAI8703335.
https://digitalcommons.unl.edu/dissertations/AAI8703335