Characterization of Cytochrome P2‐450 (20‐S) mRNA

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Abstract
Mouse liver cytochrome P2‐450 is defined as the major isosafrole‐inducible form of P‐450 which is most specific for isosafrole metabolism. λAhP‐1 represents a 15.5 × 103‐base‐pair segment of mouse genomic DNA having the cytochrome P1‐450 gene (∼ 4600 base pairs) located in the middle portion. Using various subclones as probes, we investigated the differential expression of P1‐450 mRNA and P2‐450 mRNA induction as a function of association with the Ah locus, 3‐methylcholanthrene or isosafrole dosage, tissue specificity, and developmental age. Both P1‐450 (23‐S) mRNA and P2‐450 (20‐S) mRNA induction processes are regulated by the Ah receptor. P2‐450 mRNA is about 10‐fold more sensitive than P1‐450 mRNA to induction by either 3‐methylcholanthrene or isosafrole. Phenobarbital pretreatment has no effect at all on either P1‐450 mRNA or P2‐450 mRNA. Whereas both P1‐450 mRNA and P2‐450 mRNA are induced by 3‐methycholanthrene in C57BL/6N liver, P1‐450 (23‐S) mRNA but not P2‐450 (20‐S) mRNA is induced by 3‐methylcholanthrene in C57BL/6N kidney. P1‐450 mRNA induction by 3‐methylcholanthrene is measurable in C57BL/6N liver at day 15 of gestation, and the expression becomes enhanced with increasing age. P2‐450 mRNA induction by 3‐methylcolanthrene in C57BL/6N liver appears about 7 days later during development than 3‐methylcholanthrene‐inducible P1‐450 mRNA. Both 3‐methylcholanthrene‐induced P1‐450 mRNA and P2‐450 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. P1‐450 (23‐S) mRNA and P2‐450 (20‐S) mRNA appear to hybridize to a common 5′ fragment of the P1‐450 gene.