Open AccessCharacterization of Cytochrome P 2 ‐450 (20‐S) mRNA
Author(s) -
IKEDA Toshihiko,
ALTIERI Mario,
CHEN YuanTsong,
NAKAMURA Michitoshi,
TUKEY Robert H.,
NEBERT Daniel W.,
NEGISHI Masahiko
Publication year - 1983
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1983.tb07524.x
Subject(s) - methylcholanthrene , messenger rna , microbiology and biotechnology , biology , phenobarbital , cytochrome , cytochrome p450 , gene expression , gene , biochemistry , metabolism , carcinogen , enzyme , endocrinology
Mouse liver cytochrome P 2 ‐450 is defined as the major isosafrole‐inducible form of P‐450 which is most specific for isosafrole metabolism. λAhP‐1 represents a 15.5 × 10 3 ‐base‐pair segment of mouse genomic DNA having the cytochrome P 1 ‐450 gene (∼ 4600 base pairs) located in the middle portion. Using various subclones as probes, we investigated the differential expression of P 1 ‐450 mRNA and P 2 ‐450 mRNA induction as a function of association with the Ah locus, 3‐methylcholanthrene or isosafrole dosage, tissue specificity, and developmental age. Both P 1 ‐450 (23‐S) mRNA and P 2 ‐450 (20‐S) mRNA induction processes are regulated by the Ah receptor. P 2 ‐450 mRNA is about 10‐fold more sensitive than P 1 ‐450 mRNA to induction by either 3‐methylcholanthrene or isosafrole. Phenobarbital pretreatment has no effect at all on either P 1 ‐450 mRNA or P 2 ‐450 mRNA. Whereas both P 1 ‐450 mRNA and P 2 ‐450 mRNA are induced by 3‐methycholanthrene in C57BL/6N liver, P 1 ‐450 (23‐S) mRNA but not P 2 ‐450 (20‐S) mRNA is induced by 3‐methylcholanthrene in C57BL/6N kidney. P 1 ‐450 mRNA induction by 3‐methylcholanthrene is measurable in C57BL/6N liver at day 15 of gestation, and the expression becomes enhanced with increasing age. P 2 ‐450 mRNA induction by 3‐methylcolanthrene in C57BL/6N liver appears about 7 days later during development than 3‐methylcholanthrene‐inducible P 1 ‐450 mRNA. Both 3‐methylcholanthrene‐induced P 1 ‐450 mRNA and P 2 ‐450 mRNA are detectable in DBA/2N liver; their appearance is later in development, however, and at lower concentrations than that seen with C57BL/6N liver. P 1 ‐450 (23‐S) mRNA and P 2 ‐450 (20‐S) mRNA appear to hybridize to a common 5′ fragment of the P 1 ‐450 gene.