These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Structural gene products of the Ah locus. Transcriptional regulation of cytochrome P1-450 and P3-450 mRNA levels by 3-methylcholanthrene.
    Author: Gonzalez FJ, Tukey RH, Nebert DW.
    Journal: Mol Pharmacol; 1984 Jul; 26(1):117-21. PubMed ID: 6749129.
    Abstract:
    Mouse liver cytochromes P1-450 and P3-450 represent those forms of polycylic hydrocarbon-induced P-450 most closely associated with induced aryl hydrocarbon (benzo[a] pyrene) hydroxylase and acetanilide 4-hydroxylase activity, respectively. These two proteins are controlled by the Ah receptor: C57BL/6N mice possess the high-affinity receptor; DBA/2N mice, the poor-affinity receptor. 3-Methylcholanthrene at the highest dose technically possible induces both proteins in C57BL/6N but not DBA/2N mice, whereas sufficiently high doses of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) induce both proteins in both inbred mouse strains. Plasmids containing DNA complementary to P1-450 and P3-450 mRNA, respectively, were used in an in vitro nuclear transcription assay to determine the mechanism of the induction response. In C57BL/6N mice, transcriptional rates of the P1-450 and P3-450 genes increase dramatically as early as 3 hr after 3-methylcholanthrene treatment and at 12 hr reach maximal levels of 20- and 15-fold, respectively, above control values. In contrast, no increase in either gene is found in 3-methylcholanthrene-treated DBA/2N mice. Following TCDD administration, both P1-450 and P3-450 gene transcription rates are elevated in DBA/2N mice. There is a 3- to 6-hr lag period between the early onset of enhanced transcription rates and the later rise in P1-450 and P3-450 mRNA. Basal and induced levels of P3-450 mRNA are about 5-fold greater than those of P1-450 mRNA. These data confirm that the 3-methylcholanthrene and TCDD induction responses, governed by the Ah receptor, are mediated principally through an increase in specific gene transcription.
    [Abstract] [Full Text] [Related] [New Search]